ovalbumin and Edema

IgE-mediated histamine release was studied using the method of passive peritoneal anaphylaxis (PPA) in the rat. Some beta-adrenergic stimulants markedly inhibited this reaction in vivo, the order of potency (ED50 microng/kg i.v.) of agents tested being fenoterol (6), salbutamol (40) and isoproterenol (94). Higher activity against the simultaneously measured dye extravasation suggested a dual effect of the drugs on both the cellular (inhibition of histamine release) and the vascular level. The order of potency in modifying vascular injury was, however, reversed, isoproterenol and not fenoterol being relatively more active here, as could be shown by further experiments. Inhibition of histamine release is discussed with respect to (a) methodical requirements and (b) the suggestion that beta2-receptor stimulants (fenoterol, salbutamol) are more selective than isoproterenol.

Topics: Adrenergic beta-Agonists; Anaphylaxis; Animals; Antigens; Ascitic Fluid; Cromolyn Sodium; Dextrans; Dose-Response Relationship, Drug; Edema; Evans Blue; Fenoterol; Histamine Release; Immunoglobulin E; Male; Ovalbumin; Rats; Serotonin

Topics: Animals; Anti-Inflammatory Agents; Bradykinin; Carrageenan; Cell Migration Inhibition; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Foot; Formaldehyde; Guinea Pigs; Histamine; Inflammation; Kaolin; Ovalbumin; p-Methoxy-N-methylphenethylamine; Povidone; Rabbits; Rats; Saccharomyces cerevisiae; Serotonin; Species Specificity

Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear.. To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims.. Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism.. In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes.. Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

Topics: Allergens; Animals; Anti-Allergic Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Artemisia; Candida glabrata; Cytokines; Edema; Escherichia coli; Guinea Pigs; Male; Medicine, Chinese Traditional; Medicine, Mongolian Traditional; Mice; Molecular Docking Simulation; Nasal Mucosa; Ovalbumin; Plant Extracts; Receptors, Histamine H1; Rhinitis, Allergic; Sinusitis; Staphylococcus aureus; Xylenes

The frequency of allergic diseases is constantly rising. Dysregulated production of isotype E immunoglobulins is one of the key factors behind allergic reactions and its modulation is therefore an important target for pharmacological intervention. Natural products of the pseurotin family were reported to be inhibitors of IgE production in B-cells. Mechanistic details underlying these effects are however not well understood.. In the present study, we synthesized new analogs of natural pseurotins and extensively investigated their inhibitory effects on activation, proliferation and differentiation of B-cells, as well as on the production of IgE.. Effects of two natural pseurotins (pseurotins A and D) and a collection of fully synthetic pseurotin analogs were studied on mouse B-cells stimulated by the combination of IL-4 and E. coli lipopolysaccharide. The IgE production was determined along with cell viability and cell proliferation. The phosphorylation of selected members of the STAT transcription factor family was subsequently investigated. Finally, the in vivo effect of pseurotin D on the ovalbumin-induced delayed type hypersensitivity response was tested in mice.. We discovered that several fully synthetic pseurotin analogs were able to decrease the production of IgE in stimulated B-cells with potency comparable to that of pseurotins A and D. We found that the two natural pseurotins and the active synthetic analogs inhibited the phosphorylation of STAT3, STAT5 and STAT6 proteins in stimulated B-cells, resulting in the inhibition of B-cell proliferation and differentiation into the plasma cells. In vivo, pseurotin D decreased ovalbumin-induced foot pad edema.. Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of IgE production in B-cells by linking the effect to STAT signaling, and associated modulation of B-cell proliferation and differentiation. Together with our finding that structurally simpler pseurotin analogs were able to reproduce the effects of natural pseurotins, the presented work has implications for the future research on these secondary metabolites in the context of allergic diseases.

Topics: Animals; B-Lymphocytes; Cell Differentiation; Edema; Escherichia coli; Immunoglobulin E; Immunoglobulin M; Lipopolysaccharides; Lymphocyte Activation; Male; Mice, Inbred C57BL; Ovalbumin; Phosphorylation; Plasma Cells; Pyrrolidinones; STAT Transcription Factors

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1β. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1β dependent pathways.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Edema; Male; Molecular Docking Simulation; Ovalbumin; Phytol; Rats, Wistar

A series of new isoxazole derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated.. In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined.. The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo, but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound.. MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cell Proliferation; Cells, Cultured; Edema; Female; Humans; Hypersensitivity, Delayed; Immunity, Humoral; Inflammation; Isoxazoles; Leukocytes, Mononuclear; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Ovalbumin; Phytohemagglutinins; Sheep; Tumor Necrosis Factor-alpha

Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied.. The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema.. Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th day. They were treated with either vehicle, PIP (10, 20, and 40 mg/kg, p.o.), or montelukast (10 mg/kg, p.o.) from the 14th to 20th day. On the 21st day, intranasal (OVA: 5% µl) challenge was done. Animals were evaluated for physiological parameters, biochemical parameters, spleen weight, expression of interleukins (IL-6 and IL-1β), and immunoglobin-E (IgE). Histopathology of nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were made to understand the mechanism of action.. PIP (10, 20, and 40 mg/kg, p.o.) showed a significant dose-dependent protection with respect to nasal rubbing, redness of nose, and sneezing (p < 0.001) following nasal challenge. PIP dose dependently reduced histamine, NO concentration (p < 0.001), as well as reduced expression of IL-6, IL-1β, and IgE (p < 0.001) as compared with the control group. Histopathology showed inhibition of infiltration of eosinophils and hyperplasia. It dose dependently reduced MSD and paw edema (p < 0.001).. PIP acts by mast cell-stabilizing activity, exhibits immunomodulatory and anti-inflammatory activity, thereby providing an effective treatment for AR.

Topics: Acetates; Alkaloids; Animals; Anti-Allergic Agents; Benzodioxoles; Biomarkers; Cell Degranulation; Cyclopropanes; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Eosinophils; Histamine; Immunoglobulin E; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Mast Cells; Nitric Oxide; Ovalbumin; Piperidines; Polyunsaturated Alkamides; Quinolines; Rhinitis, Allergic; Spleen; Sulfides; Time Factors

Telfairia occidentalis (Cucurbitaceae) is a tropical vine grown in West Africa as a leaf vegetable and for its edible seeds. The plant is noted to have healing properties. It is used as a blood tonic to revive weak/ill individuals and its use by sickle cell patients has been documented. In this study, the antinociceptive activity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was evaluated using the acetic acid-induced writhing, formalin, tail clip, and hot plate tests in mice. The carrageenan- and egg albumin-induced rat paw edema tests were used to evaluate the anti-inflammatory action. The extract (50-400 mg/kg, p.o.) produced significant (P<.05) dose-dependent inhibition of pain response elicited by acetic acid and formalin while also increasing the nociceptive reaction latency in the tail clip and hot plate tests. In respect of anti-inflammatory activity, the extract elicited significant (P<.05) time and dose-dependent inhibition of edema development in the carrageenan and egg albumin tests. Peak effects of TO in the models were generally comparable with the effects of the standard drugs (acetylsalicylic acid, morphine, indomethacin, and chlorpheniramine) used. Phytochemical screening of the extract revealed the presence of tannins, saponins, phlobatannins, and anthraquinones. The extract did not produce any mortality and visible signs of delayed toxicity when administered orally up to 2000 mg/kg. The LD50 (i.p.) was estimated to be 4073.80 mg/kg. The results obtained in this study suggest that TO possesses antinociceptive and anti-inflammatory activities possibly mediated through peripheral and central mechanisms involving inhibition of release and/or actions of vasoactive substances and prostaglandins.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Cucurbitaceae; Edema; Female; Formaldehyde; Hot Temperature; Male; Mice; Ovalbumin; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plant Leaves

Recent studies have shown that lectins are promising tools for use in various biotechnological processes, as well as studies of various pathological mechanisms, isolation, and characterization of glycoconjugates and understanding the mechanisms underlying pathological mechanisms conditions, including the inflammatory response. This study aimed to purify, characterize physicochemically, and predict the biological activity of Canavalia oxyphylla lectin (CoxyL) in vitro and in vivo. CoxyL was purified by a single-step affinity chromatography in Sephadex® G-50 column. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the pure lectin consists of a major band of 30 kDa (α-chain) and two minor components (β-chain and γ-chain) of 16 and 13 kDa, respectively. These data were further confirmed by electrospray ionization mass spectrometry, suggesting that CoxyL is a typical ConA-like lectin. In comparison with the average molecular mass of α-chain, the partial amino acid sequence obtained corresponds to approximately 45% of the total CoxyL sequence. CoxyL presented hemagglutinating activity that was specifically inhibited by monosaccharides (D-glucose, D-mannose, and α-methyl-D-mannoside) and glycoproteins (ovalbumin and fetuin). Moreover, CoxyL was shown to be thermostable, exhibiting full hemagglutinating activity up to 60°C, and it was pH-sensitive for 1 h, exhibiting maximal activity at pH 7.0. CoxyL caused toxicity to Artemia nauplii and induced paw edema in rats. This biological activity highlights the importance of lectins as important tools to better understand the mechanisms underlying inflammatory responses.

Topics: Amino Acid Sequence; Animals; Artemia; Canavalia; Chromatography, Affinity; Dextrans; Edema; Electrophoresis, Polyacrylamide Gel; Fetuins; Hemagglutination; Hindlimb; Hydrogen-Ion Concentration; Inflammation; Male; Molecular Sequence Data; Molecular Weight; Monosaccharides; Ovalbumin; Plant Lectins; Protein Stability; Protein Subunits; Rats; Rats, Wistar; Seeds

Zanthoxylum bungeanum Maxim seed (ZBMS) has been used in Traditional Chinese Medicine (TCM) as an ingredient of polyherbal formulations for the treatment of inflammation and asthma. The aim of this study was to analyze the major composition and to evaluate the anti-asthma activity of ZBMS.. Some murine models including acetylcholine/histamine-induced asthma, ovalbumin-induced airway inflammation, ear edema and toe swelling measurement, citric acid-induced cough, and anti-stress abilities were investigated to fully study the anti-asthma activity of ZBMS.GC chromatography was also performed to analyze the major fatty acid composition of ZBMS.. The results demonstrated that the major fatty acid composition of ZBMS includes oleic acid (20.15%), linoleic acid (26.54%), and α-linolenic acid (30.57%), which was the leading component of ZBMS, and that the total fatty acid content of ZBMS was 77.27%. The murine models demonstrated that ZBMS displays a protective effect on guinea pig sensitization, a dose-dependent inhibition of the increases in RL and decreases in Cdyn, which resulted in the relief of auricle edema and toe swelling in mice and anti-stress activity.. Our results validate the traditional use of ZBMS for the treatment of asthma and other inflammatory joint disorders, and suggest that ZBMS has potential as a new therapeutic agent for asthma management.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Guinea Pigs; Inflammation; Male; Medicine, Chinese Traditional; Mice; Ovalbumin; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Zanthoxylum

This article describes the design, synthesis, and biological evaluation of new indole-based cytosolic phospholipase A2α (cPLA2α, a group IVA phospholipase A2) inhibitors. A screening-hit compound from our library, (E)-3-{4-[(4-chlorophenyl)thio]-3-nitrophenyl}acrylic acid (5), was used to design a class of 3-(1-aryl-1H-indol-5-yl)propanoic acids as new small molecule inhibitors. The resultant structure-activity relationships studied using the isolated enzyme and by cell-based assays revealed that the 1-(p-O-substituted)phenyl, 3-phenylethyl, and 5-propanoic acid groups on the indole core are essential for good inhibitory activity against cPLA2α. Optimization of the p-substituents on the N1 phenyl group led to the discovery of 56n (ASB14780), which was shown to be a potent inhibitor of cPLA2α via enzyme assay, cell-based assay, and guinea pig and human whole-blood assays. It displayed oral efficacy toward mice tetradecanoyl phorbol acetate-induced ear edema and guinea pig ovalbumin-induced asthma models.

Topics: Animals; Area Under Curve; Asthma; Cytosol; Dogs; Drug Design; Edema; Enzyme Inhibitors; Female; Group IV Phospholipases A2; Guinea Pigs; Haplorhini; Humans; Indoles; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Models, Chemical; Molecular Structure; Ovalbumin; Propionates; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; U937 Cells

The inflammation process is a coordinated response of the organism related to immune response with release of pro-inflammatory substances, as nitric oxide, TNF-α and IL-1β. In this work, a series of lipophilic amino alcohols were evaluated on RAW264.7 and primary macrophages for the modulation of nitric oxide and TNF-α. The most potent compounds were submitted to the treatment of BALB/c mice and evaluation of the carrageenan-induced paw edema and TNF-α and IL1-β release in the paws and anti-OVA delayed type hypersensitivity reaction. RAW264.7 and primary macrophages were incubated in the presence of amino alcohols at different concentrations (1, 0.5, 0.05 and 0.005 μg mL(-1)). All tested compounds were not cytotoxic, however the inhibition of NO and TNF-α were observed only in RAW264.7 cultures. The NO production were reduced in 100% for all compounds, but only the compounds 4a and 4b expressively reduced the TNF-α release (67% and 92% respectively). On the carrageenan-induced paw edema, the compound 4b treatment showed reduction of edema, TNF-α and IL-1β as efficient as dexamethasone treatment. Meanwhile, the compound 4a treatment showed only slight reduction of paw edema. In the anti-OVA DTH reaction, both compounds showed reduction in the paw edema as effective as dexamethasone. In function of the observed results in vitro and in the acute and anti-OVA inflammation of mice paw edema compound 4b showed promissory anti-inflammatory properties.

Topics: Allergens; Amino Alcohols; Animals; Anti-Inflammatory Agents; Carrageenan; Cell Line; Cells, Cultured; Edema; Foot; Hypersensitivity, Delayed; Interleukin-1beta; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Ovalbumin; Tumor Necrosis Factor-alpha

The anti-inflammatory activity of Canavalia seed lectins (Canavalia gladiata [CGL], Canavalia maritima [ConM] and Canavalia brasiliensis [ConBr]) was evaluated by intravenous administration in rats. In non-sensitized rats, cellular edema elicited by carrageenan was reduced (45-51 %) by ConM and (44-59 %) by CGL. Osmotic edema elicited by dextran was reduced by ConM and CGL in 27 % and 29 %. ConM and CGL reduced the edema elicited by L-arginine in 53 % and that of prostaglandin E2 in 48 % and 36 %. Leukocyte migration elicited by carrageenan was reduced in 49 % by ConM and in 55 % by CGL (attenuated in 4× by glucose) and peritoneal TNF-α content in 82 %. In rats sensitized, ConM inhibited the paw edema and leukocyte migration elicited by ovalbumin in 34 % and 70 %. ConM and CGL are anti-inflammatory, mainly in cellular events mediated by prostaglandin E₂, nitric oxide and TNF-α in non-sensitized rats. However, only ConM is anti-inflammatory in sensitized rats. CGL effect involves the lectin domain.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginine; Carrageenan; Cell Movement; Dextrans; Dinoprostone; Edema; Inflammation; Leukocytes; Ovalbumin; Plant Lectins; Rats; Tumor Necrosis Factor-alpha

Nilotinib is a new orally bioavailable potent tyrosine kinase inhibitor that is used for the treatment of BCR-ABL-positive chronic myelogenous leukemia. However, its effect on mast cell-mediated anaphylactic reaction is still not known. The present study aimed to investigate the effect of nilotinib on the anaphylactic allergic reaction and study its possible mechanism(s) of action. Nilotinib administration prevented systemic anaphylaxis in mice, mediated by compound 48/80, in a dose- and time-dependent manner. Also, nilotinib significantly inhibited (P<0.05) allergic paw edema in rats. Furthermore, nilotinib significantly decreased (P<0.05) the IgE-mediated passive cutaneous anaphylaxis in a dose dependent manner. In addition, nilotinib dose-dependently reduced histamine release from the rat peritoneal mast cells activated either by compound 48/80 or by ovalbumin. Moreover, nilotinib attenuated the secretion of pro-inflammatory cytokine, tumor necrosis factor (TNF)-α expression in the rat peritoneal mast cells. These findings provide evidence that nilotinib inhibits mast cell-derived immediate-type allergic reactions and so it could be a candidate as an anti-allergic agent.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Cytokines; Edema; Histamine Release; Hypersensitivity; Immunoglobulin E; Male; Mast Cells; Mice; Ovalbumin; p-Methoxy-N-methylphenethylamine; Protein-Tyrosine Kinases; Pyrimidines; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

To investigate the role of cannabinoid receptor-2 (CB2) in allergic inflammation in CB2 knockout (CB2-KO) mice.. The swelling reaction of the pinna to various stimuli was compared between CB2-KO and wild-type (WT) mice in terms of edema and acanthosis.. Ear swelling induced by repeated application of 2,4-dinitrofluorobenzene in CB2-KO mice was significantly decreased compared with that in WT mice. In an ovalbumin model, pinna edema was significantly suppressed in CB2-KO mice in comparison with that in WT mice. The contribution of CB2 to edema was investigated in a more extreme dermatitis model using oxazolone. Delayed-type hypersensitivity reactions in this model were also suppressed in CB2-KO mice. In each of these three different allergic dermatitis models, there was a significant decrease in edema and acanthosis in CB2-KO mice compared with WT mice.. These results clearly demonstrate that CB2 and its endogenous ligands participate not only in the acute, edematous phase of allergic dermatitis, but also in the chronic irreversible acanthosis reaction.

Topics: Animals; Dermatitis; Disease Models, Animal; Edema; Hypersensitivity, Delayed; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Oxazolone; Receptor, Cannabinoid, CB2

Nanostructured lipid carriers (NLC)-based gel was developed as potential topical system for flurbiprofen (FP) topical delivery. The characterizations of the prepared semisolid formulation for topical application on skin were assessed by means of particle size distribution, zeta potential analysis, X-ray analysis, in vitro percutaneous penetration, rheological study, skin irritation test, in vivo pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained within the colloidal range and it was uniformly dispersed after suitably gelled by carbopol preparation. It was indicated in vitro permeation studies through rat skin that FP-NLC-gel had a more pronounced permeation profile compared with that of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for all NLC-gels after storage at three different temperatures. No oedema and erythema were observed after administration of FP-NLC-gel on the rabbit skin, and the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum concentration in plasma was 29.44 μg/ml and 2.49 μg/ml after oral and topical administration, respectively. While the amount of drug accumulated in skin after topical application was much higher than oral application. In conclusion, NLC-based gel could be a promising vehicle for topical delivery of FP.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Carriers; Edema; Fatty Acids; Flurbiprofen; Gels; In Vitro Techniques; Male; Nanostructures; Ovalbumin; Particle Size; Rats; Rats, Wistar; Skin; Skin Absorption; Skin Irritancy Tests; Surface-Active Agents; Triglycerides

Airway hyperreactivity is characterized by increased responsiveness to bronchoconstrictor stimuli and it is hallmark of asthma. Adenosine is an ubiquitous signaling nucleoside resulting from ATP catabolism, whose extracellular levels increase following cellular damage or stress. Adenosine plays a role in asthma; asthmatics, but not normal subjects, present bronchoconstriction following inhalation of adenosine or of its precursor, adenosine-5'-monophosphate, most likely via adenosine A(2B) receptor on mast cells. However, the mechanism underling the increased airway smooth muscle sensitivity to adenosine in asthmatics remains to be elucidated. Early experimental studies suggested the involvement of A(1) receptor; this hypothesis has been confirmed by more recent studies on guinea pigs and is corroborated by the finding of an increased adenosine A(1) expression on asthmatic bronchial tissues. Brown Norway rats, the strain usually used to assess asthma models, develop hyperresponsiveness to adenosine 3h following allergen challenge, but not 24h thereafter, without involvement of A(1) receptor. Here, we investigated the role of adenosine A(1) receptor in sensitized Wistar rats showing airway hyperresponsiveness 24h following allergen challenge. We found that on bronchi of sensitized Wistar rats challenged with allergen there is an increased adenosine A(1) receptor expression on smooth muscle that is responsible for hyperresponsiveness to adenosine and ovalbumin.

Topics: Adenosine; Adenosine A1 Receptor Antagonists; Allergens; Animals; Bronchi; Edema; Gene Expression Regulation; Hypersensitivity; Immunization; Male; Ovalbumin; Rats; Rats, Wistar; Receptor, Adenosine A1; Time Factors

Dietary proteins play an important role in the regulation of systemic immune response, in a phenomenon known as oral tolerance (OT). To evaluate the effects of OT on a murine model of type II collagen (CII) plus ovalbumin (OVA)-induced arthritis (CIA), mice were fed with OVA either before or after CIA induction. OT significantly reduced the paw edema and synovial inflammation, as well as serum levels of anti-CII, the ex vivo proliferation and inflammatory cytokine production by spleen cells from CIA mice. The frequencies of Foxp3(+) and IL-10(+) cells were higher, whereas IFNγ(+) cells and IL-17(+) cells were lower, among gated CD4(+) spleen T cells from tolerized CIA mice than in those from non-tolerized CIA mice. Adoptive transfer of tolerogenic dendritic cells (DCs) before CIA induction mimics the effects observed in the OT. We demonstrate here that bystander suppression induced by OT can modify the course of CIA and tolerogenic DCs play a role this phenomenon.

Topics: Adoptive Transfer; Animals; Arthritis, Experimental; Bystander Effect; Coculture Techniques; Collagen Type II; Cytokines; Dendritic Cells; Dietary Proteins; Edema; Forkhead Transcription Factors; Immune Tolerance; Immunization; Interferon-gamma; Interleukin-10; Interleukin-17; Isoantibodies; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Specific Pathogen-Free Organisms; Spleen

To evaluate the anti-inflammatory property of leaves of Sansevieria liberica Ger. and Labr. and to ascertain the toxicity and phytochemical profiles of the extract of the leaves.. The juice from the fresh leaves was expressed manually and lyophilized. The crude extract (CE) was then fractionated into n-hexane fraction (HF), chloroform fraction (CF), ethylacetate fraction (EF) and methanol fraction (MF). The crude extract (CF) and the fractions were screened for anti-inflammatory activity using egg albumen-induced paw (systemic) edema in rats as a measure of acute inflammation. The toxicity test and phytochemical screening were done using standard procedures.. The CE and the fractions significantly (P<0.05) inhibited the development of paw edema induced by egg albumen in rats. The potency/activity of the CE and the fractions increased in the order HF>CE>MF>CF>EF, with the CE and HF at 400 mg/kg exhibiting inhibition comparable to that obtained with 5 mg/kg diclofenac sodium. Acute toxicity test on CE established an oral and intraperitoneal LD(50) of > 5 000 mg/kg in mice. Phytochemical screening of the CE and the fractions showed the presence of various bioactive substances such as alkaloids, saponins, flavonoids, terpenoids, steroids, glycosides, reducing sugars, tannins, resins, carbohydrates, proteins, acidic compounds, fats and oils.. The results of the study showed that the leaves of Sansevieria liberica Ger and Labr. possess anti-inflammatory effects which may be due to its bioactive constituents. Further purification on these bioactive constituents may result in the development of potent anti-inflammatory agent with low toxicity and better therapeutic index.

Topics: Animals; Disease Models, Animal; Edema; Hindlimb; Ovalbumin; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Sansevieria

Violacein was isolated from Chromobacterium violaceum, a soil Gram negative bacterium collected from the forest water body soil sample of Kolli Hills; Tamil Nadu, India. In the present study the immunomodulatory, analgesic and antipyretic activities of violacein were investigated in wistar rats and mice. Analgesic effect was evaluated by acetic acid- induced writhing, formalin induced paw licking and hotplate tests. Immunomodulatory effect was investigated by using ovalbumin- induced active paw anaphylaxis and sheep red blood cells (SRBC)-induced DTH tests. Antipyretic activity was evaluated by yeast- induced hyperpyrexia in rats. The anti- oedema effect was compared with indomethacin. Violacein inhibited 42.9% of ovalbumin- induced edema. Further we found that violacein (40mg/kg b.w.) reduced the edema induced by sheep red blood cells. Violacein also produced significant (p<0.05) analgesic activity in acetic acid induced writhing response, formalin induced paw licking response and hot plate analysis. Treatment with violacein showed a significant (p<0.05) dose-dependent reduction in pyrexia in rats. The results suggest that violacein possesses potent immunomodulatory, analgesic and antipyretic activities.

Topics: Acetic Acid; Analgesics; Anaphylaxis; Animals; Behavior, Animal; Chromobacterium; Dose-Response Relationship, Drug; Edema; Erythrocytes; Female; Fever; Formaldehyde; Hot Temperature; Hypersensitivity; Hypersensitivity, Delayed; Immunologic Factors; India; Indoles; Indomethacin; Male; Mice; Ovalbumin; Pain; Rats; Rats, Wistar; Sheep; Yeasts

There is growing evidence that chemokines recruit leukocytes in allergic, inflammatory and immune responses. CC chemokine receptor 4 (CCR4) is implicated as a preferential marker for T helper 2 cells, and the cells selectively respond to CC chemokine ligand 17 (CCL17) and CCL22. We searched for compounds having a profile as a CCR4 antagonist from an in-house library and have previously reported that 3-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}quinazoline-2,4(1H,3H)-dione (named RS-1154) was capable of significantly inhibiting the binding of [(125) I]CCL17 to human CCR4-expressing CHO cells. From further synthesis of its derivatives, we newly focused on 3-(isobutyrylamino)-N-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}benzamide (RS-1269), which showed potency comparable to RS-1154 in inhibiting CCL17-induced migration of DO11.10 mice-derived T helper 2 cells with an IC(50) value of 5.5 nM in vitro. We then investigated the pharmacological effects of RS-1269 on ovalbumin-induced ear swelling and lipopolysaccharide-induced endotoxic shock in mice. The ear thickness was significantly decreased by oral administration of RS-1269 at the dose of 30 mg/kg. Treatment with lipopolysaccharide significantly increased the serum level of tumour necrosis factor-α. Compared with an anti-CCL17 antibody, RS-1269 significantly inhibited the production at the dose of 100 mg/kg. These results raise the possibility that RS-1269 or one of its derivatives has potential to serve as a prototype compound to develop therapeutic agents for atopic dermatitis and inflammatory diseases.

Topics: Administration, Oral; Animals; Benzamides; Chemotaxis, Leukocyte; Ear, External; Edema; Female; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Transgenic; Morpholines; Ovalbumin; Receptors, CCR4; Shock, Septic; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor-alpha

Methotrexate (MTX) encapsulated microspheres release MTX in the joint in a slow, controlled manner following intra-articular injection in healthy rabbits. The objective of this study was to determine the pharmacokinetics of MTX and to evaluate the efficacy following intra-articular treatment of MTX-loaded microspheres in an antigen-induced inflammatory arthritis rabbit model.. Arthritis was induced in both knee joints of rabbits using ovalbumin. Rabbits were intra-articularly treated with MTX solution or MTX microspheres and plasma concentrations of MTX were determined in the first 8 h following intra-articular treatment. Rabbits were killed 14 days following treatment and histological analysis of rabbit joints was conducted to determine efficacy.. Arthritis was successfully induced in the joints of rabbits with the observation of histopathological features resembling rheumatoid arthritis. No significant differences were detected between MTX solution and MTX microspheres treated groups compared to phosphate buffered saline (control) animals.. MTX microspheres effectively delivered the drug to the intra-articular space. However, a high degree of inter-animal variability, the severity of the disease induced and insufficient length of the observation period were suggested to be possible causes for the lack of therapeutic responses to MTX-loaded microspheres treatment.

Topics: Animals; Antirheumatic Agents; Arthritis; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Edema; Female; Hindlimb; Injections, Intra-Articular; Joints; Methotrexate; Microspheres; Ovalbumin; Rabbits

Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Antioxidants; Biphenyl Compounds; Bronchoalveolar Lavage Fluid; Calcium; Edema; Eosinophil Peroxidase; Erythrocytes; Histamine; Histamine Antagonists; Lipid Peroxidation; Mast Cells; Mice; Mice, Inbred BALB C; Onions; Ovalbumin; Picrates; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Superoxide Dismutase

The role of CD8(+) T cells in oral tolerance remains unclear. To address this, we developed a model to induce CD8(+) Tregs by feeding the major histocompatibility complex class I immunodominant epitope of OVA, OVA((257-264)). OVA((257-264)) feeding induced tolerance similar to that observed in OVA protein-fed mice, capable of suppressing the production of Th1 and Th17 cytokines and inhibiting a Th1-driven delayed-type hypersensitivity response following immunization with whole OVA (wOVA) protein. OVA((257-264)) peptide-induced suppression could be transferred to naive mice with CD8(+) cells, but not CD8-depleted cells, isolated from mesenteric lymph nodes of peptide-fed mice. Interestingly, while capable of inhibiting Th1 and Th17 responses, OVA((257-264)) feeding could not suppress any feature of a Th2 inflammatory response, though OVA protein feeding could, suggesting that these cells function through a different mechanism than their CD4(+) counterparts generated in response to feeding with wOVA. Thus, CD8(+) T cells are functionally capable of mediating tolerance to Th1 and Th17 responses.

Topics: Administration, Intranasal; Administration, Oral; Adoptive Transfer; Alveolitis, Extrinsic Allergic; Animals; Antigens; CD8-Positive T-Lymphocytes; Desensitization, Immunologic; Ear, External; Edema; Immune Tolerance; Immunization; Immunodominant Epitopes; Injections, Intradermal; Lymphocyte Cooperation; Mice; Mice, Inbred C57BL; Models, Immunological; Ovalbumin; Peptide Fragments; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Schinus is a genus of the Anacardiaceae family and contains Schinus terebinthifolius, the Brazilian pepper tree that is widely used in folk medicine. We investigate the anti-allergic activity of the ethyl acetate fraction of S. terebinthifolius Raddi (ST fraction). HPLC analysis reveled that gallic acid, methyl gallate and 1,2,3,4,6-pentagalloylglucose are the major aromatic components of the fraction. Oral pre-treatment with the ST fraction (100 mg/kg) significantly inhibited paw edema induced by compound 48/80 (100 ng/paw) and to a lesser extent, the allergic paw edema (OVA, 3 microg/paw). The ST fraction (100 and 200 mg/kg) also inhibited the edema induced by histamine (100 microg/paw), preventing mast cell degranulation and, consequently, histamine release in Wistar rat peritoneal mast cells induced by C 48/80 (5 microg/mL). This histamine inhibition was also observed after mast cell pre-treatment with both methyl gallate and 1,2,3,4,6-pentagalloylglucose (100 microg/mL), the isolated compounds from the ethyl acetate fraction. Pre-treatment with the ST fraction (100 mg/kg) significantly inhibited total leukocyte and eosinophil accumulation in pleural cavities 24 h after the intrathoracic injection of OVA (12.5 microg/cavity). This effect was related to the inhibition of CCL11/eotaxin and CCL5/RANTES in pleural lavage fluid. Pre-treatment with this fraction (100 mg/kg) failed to reduce the cell influx that was observed after LPS-injection into pleural cavity (250 ng/cavity). These findings demonstrate the anti-allergic effect of the ST fraction, which includes the inhibition of edema formation and histamine release caused by mast cell degranulation and eosinophil influx into the pleural cavity probably reflected by the decreased levels of chemokines in recovered pleural lavage fluid.

Topics: Anacardiaceae; Animals; Anti-Allergic Agents; Chemokines; Edema; Histamine; Histamine Release; Hypersensitivity; Immunoglobulin E; Lipopolysaccharides; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Plant Leaves; Pleurisy; Promethazine; Rats; Rats, Wistar

Epidemiological studies suggest that obesity is associated with the impairment of immunity. However, there is no experimental evidence that obesity prejudices immune responses.. This study was designed to determine the effects of obesity on contact hypersensitivity (CHS) response using a diet-induced obese (DIO) mouse model.. The effect of high fat diet (HFD) on CHS response to trinitrochlorobenzene (TNCB) was assessed by ear swelling, cytokine production, functional analysis of epidermal Langerhans cells, and adoptive transfer of immune cells. Immune response to ovalbumin was also analyzed in DIO mice.. C57BL/6 mice but not BALB/c mice that fed with HFD for 4 weeks or more became obese and showed impaired CHS response, although both strain of mice showed enhanced irritant response to TNCB. CHS response was slightly impaired when C57BL/6 mice fed with HFD for 1 or 2 weeks. This suggests that diet-induced obesity or the HFD itself impairs the CHS response in the susceptible mice. The adoptive transfer of immune cells from DIO mice sensitized with TNCB to naïve mice failed to show vigorous CHS, which suggests dysfunction of an afferent phase of CHS in DIO mice. However, the number and allo-stimulating ability of epidermal Langerhans cells were comparable between DIO mice and lean mice. In addition, the immune response to ovalbumin (delayed type hypersensitivity, and antigen-dependent production of antibodies and cytokine) was preserved in DIO mice.. These results suggest that the diet-induced obesity or the HFD only partially impairs immunity in the susceptible mice.

Topics: Adoptive Transfer; Animals; Cytokines; Dermatitis, Allergic Contact; Dietary Fats; Disease Models, Animal; Edema; Female; Hypersensitivity, Delayed; Langerhans Cells; Leptin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Obesity; Ovalbumin; Picryl Chloride; Species Specificity; T-Lymphocytes; Time Factors

Fructooligosaccharides (FOS) in prebiotic foods can alter intestinal immune responses. The combination of probiotics with oligosaccharides has been reported to alter intestinal flora and suggested to be beneficial against food allergy in humans.. All male Nc/jic mice used in this 8-week study were 6 weeks of age and were allotted to the following three groups: (1) the nonsensitization group; (2) the ovalbumin (OVA) sensitization +5% fructose-containing control food administration group; and (3) the OVA sensitization +5% FOS-containing food administration group. Duodenal tissues were collected and then immunohistochemically stained with monoclonal antibodies to CCR4 and CCR5. The number of mast cells and the villus edema formation rate in the duodenum were determined by image analysis.. The number of CCR4-positive cells increased significantly in Group 2 as compared with Group 1 and tended to decrease in Group 3 as compared with Group 2. Relatively few CCR5-positive cells were observed in the duodenum. FOS tended to reduce the number of CCR4-positive cells but significantly reduced the number of mast cells and the edema formation rate in the duodenum.. This study demonstrated a correlation between the number of CCR4-positive cells and villus edema formation rate. Therefore, FOS, which we inferred to show antiallergic activity for food allergy in this study and which has already been established to be safe for use as food in humans, can be considered to be potentially useful for the prevention of food allergy in pediatric patients with allergy.

Topics: Animals; Anti-Allergic Agents; Cell Count; Disease Models, Animal; Duodenal Diseases; Duodenum; Edema; Food Hypersensitivity; Immunoglobulin E; Male; Mast Cells; Mice; Microvilli; Oligosaccharides; Ovalbumin; Probiotics; Receptors, CCR4; Receptors, CCR5; Receptors, Chemokine; T-Lymphocytes, Helper-Inducer

To examine the expression of Foxp3 on CD8+ T cells in the spleen during anterior chamber-associated immune deviation (ACAID).. Ovalbumin (OVA) was injected into the anterior chamber (AC) of C57BL/6 mice, and the delayed-type hypersensitivity (DTH) response was measured to evaluate the development of ACAID. The suppressive effect of CD8+ T cells in ACAID mice was determined by a local adoptive transfer (LAT) assay. Flow cytometry was used to assay the frequency of CD8+ Foxp3+ T cells from normal mice, ACAID mice, and control mice receiving an AC injection of PBS (PBS-AC-injected mice). These frequencies were also tested after polyclonal or specific antigen stimulation. The mRNA level of Foxp3 in CD8+ splenocytes from different groups with or without stimulation were determined by reverse transcription-polymerase chain reaction.. OVA injection into the AC induced ACAID, and CD8+ T cells from ACAID mice inhibited the ear-swelling response by OVA-primed responder cells in LAT assay. Flow cytometry analysis showed that the frequency of CD8+ Foxp3+ cells in splenocytes was upregulated in ACAID mice following polyclonal or specific antigen stimulation. Foxp3 mRNA was only detected in CD8+ T cells from ACAID mice after polyclonal stimulation.. An upregulated Foxp3 expression in CD8+ T cells is associated with the development of ACAID, suggesting an involvement of CD8+ Foxp3+ T cells in this model of immune tolerance.

Topics: Adoptive Transfer; Animals; Anterior Chamber; Antigens; CD8-Positive T-Lymphocytes; Cells, Cultured; Ear Diseases; Edema; Flow Cytometry; Forkhead Transcription Factors; Hypersensitivity, Delayed; Immune Tolerance; Lymphocyte Activation; Lymphocyte Count; Mice; Mice, Inbred C57BL; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spleen; Up-Regulation

A 95% ethanol extract from whole aerial parts of Euphorbia hirta (EH A001) showed antihistaminic, antiinflammatory and immunosuppressive properties in various animal models. EH A001 inhibited rat peritoneal mast cell degranulation triggered by compound 48/80. It significantly inhibited dextran-induced rat paw edema. EH A001 prevented eosinophil accumulation and eosinophil peroxidase activity and reduced the protein content in bronchoalveolar lavage fluid (BALF) in a 'mild' model of asthma. Moreover, the CD4/CD8 ratio in peripheral blood was suppressed. EH A001 attenuated the release of interleukin-4 (IL-4) and augmented interferon-gamma (IFN-gamma) in ovalbumin-sensitized mouse splenocytes. The results were compared with the effects of known compounds, ketotifen, cetirizine and cyclophosphamide. These findings demonstrated that Euphorbia hirta possessed significant activity to prevent early and late phase allergic reactions.

Topics: Animals; Bronchoalveolar Lavage Fluid; CD4-CD8 Ratio; Cytokines; Edema; Eosinophil Peroxidase; Eosinophils; Euphorbia; Histamine Antagonists; Hypersensitivity; Leukocyte Count; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Rats; Rats, Wistar; Spleen

An effect of apiogalacturonanic pectin of duckweed Lemna minor L. (lemnan LM) was studied on the inflammatory response to ovalbumin injected intradermally into the footpad of control and ovalbumin-fed mice. Lemnan LM (1-2 mg per mouse) was found to enhance by as much as 50-60% the footpad swelling in control mice. Oral administration of ovalbumin was shown to result in sensitization that increased inflammation. Ovalbumin admixed with lemnan was found to increase by two-fold footpad edema in comparison with the mice receiving ovalbumin alone. Apple pectin used as a reference compound failed to influence the inflammatory reaction. Degradation of lemnan was performed to elucidate the active region of the polysaccharide macromolecule. The apiogalacturonanic fragment (LMP) obtained using a digestion of lemnan LM with pectinase was shown to increase the footpad response in both control and ovalbumin-fed mice. Fragment LMPH deprived of some terminal apiose residues as a result of partial acidic hydrolysis failed to have an effect on the inflammatory response.Thus, the data obtained reveal an enhancement by lemnan of the inflammatory response. The ramified apiogalacturonan seemed to be the active region of the lemnan macromolecule.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Araceae; Edema; Male; Mice; Ovalbumin; Pectins; Phytotherapy; Plant Extracts

Chondroitin sulfate (CS) was administered orally to BALB/c mice immunized intraperitoneally with ovalbumin (OVA) and/or dinitrophenylated OVA. The titers of antigen-specific IgE and IgG1 in mouse sera were determined. The antigen-specific IgE production by mice fed ad libitum with CS was significantly inhibited. We also examined the effect of feeding CS on immediate-type hypersensitivity. One hour after antigen stimulation, the ears of mice fed with CS swelled less than those of the control mice. Furthermore, the rise in serum histamine in the mice fed with CS under active systemic anaphylaxis was significantly lower than that in the controls. We next examined the pattern of cytokine production by splenocytes from mice followed by re-stimulation with OVA in vitro. The splenocytes from the mice fed with CS produced less interleukin (IL)-5, IL-10, and IL-13 than those from the control group. In contrast, the production of interferon-gamma and IL-2 by the splenocytes of mice fed with CS was not significantly different from those in the control mice. In addition, the production of transforming growth factor-beta from the splenocytes of mice fed with CS was significantly higher than that of the control mice. Furthermore, we showed that the percentages of CD4(+) cells, CD8(+) cells, and CD4(+)CD25(+) cells in the splenocytes of mice fed with CS are significantly higher than those of the control. These findings suggest that oral intake of CS inhibits the specific IgE production and antigen-induced anaphylactic response by up-regulating regulatory T-cell differentiation, followed by down-regulating the Th2 response.

Topics: Administration, Oral; Animals; Chondroitin Sulfates; Ear; Edema; Hypersensitivity; Immunoglobulin E; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

Inflammatory effects in the rat lung have been investigated, non-invasively by MRI, at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (LPS) challenges. Six hours after challenge with OA, a strong, even inflammatory signal was present around the periphery of the lung in a region corresponding to the pleura. Histological analysis confirmed the presence of marked edema associated with the pleural cavity of OA-treated animals. Lower levels of pleural edema were observed in MRI and histological evaluation of LPS-treated animals and no abnormality was observed in actively sensitized and naïve, saline-treated groups. Diffuse edematous signals were detected in the lung 3 and 6 h after challenge with OA or LPS; the signal volumes were larger at both time points following OA instillation. Bronchoalveolar lavage (BAL) fluid analysis performed 6 h after challenge revealed increased levels of protein and greater cellular activation in OA- than in LPS-treated animals. Furthermore, increased levels of peribronchial edema were found by histology 6 h after OA. BAL fluid and histological assessments demonstrated that the inflammatory signals were due to edema and not mucus as no significant changes in BAL mucin concentrations or differences in goblet cells were identified between OA or LPS challenge and their respective vehicle groups. Our data show that MRI is able to detect, non-invasively, inflammatory signals in both the lung and the pleura in spontaneously breathing animals, highlighting its potential to study the consequences of pulmonary insults on both sites.

Topics: Acute Disease; Animals; Bronchoalveolar Lavage Fluid; Edema; Inflammation; Lipopolysaccharides; Magnetic Resonance Imaging; Male; Ovalbumin; Pleura; Pleural Diseases; Rats; Rats, Inbred BN; Respiratory Tract Diseases

We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.

Topics: Aminopyridines; Animals; Anti-Allergic Agents; Antigens; Cromolyn Sodium; Cyclosporine; Dinitrobenzenes; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Edema; Haptens; Hindlimb; Hypersensitivity, Delayed; Male; ortho-Aminobenzoates; Ovalbumin; Passive Cutaneous Anaphylaxis; Promethazine; Pyridines; Pyrimidinones; Quinolones; Rats; Rats, Wistar

The inhibition of prostaglandin (PG) synthesis is at the center of current anti-inflammatory therapies. Because cyclooxygenase-2 (COX-2) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of multiple PGs, there is currently a strong focus on characterizing the role of the different PGs in the inflammation process and development of arthritis. Evidence to date suggests that both PGE(2) and PGI(2) act as mediators of pain and inflammation. Most of the data indicating a role for PGI(2) in this context have been generated in animal models of acute pain. Herein, we describe the role of PGI(2) in models of osteoarthritis (OA) and rheumatoid arthritis using a highly selective PGI(2) receptor (IP, Ptgir) antagonist and IP receptor-deficient mice. In the rat OA model using monoiodoacetate injection into the knee joint, the IP antagonist reduced pain with an efficacy approaching that of the NSAID diclofenac. In a chronic model of inflammatory arthritis, collagen-antibody induced arthritis model in mice, IP receptor-deficient mice displayed a 91% reduction in arthritis score. Interestingly, pretreatment with the IP [N-[4-(imidazolidin-2-ylideneamino)-benzyl]-4-methoxy-benzamide] antagonist in this model also caused a significant reduction of the symptoms, whereas administration of the compound after the initiation of arthritis had no detectable effect. Our data indicate that, in addition to its role in acute inflammation, PGI(2) is involved in the development of chronic inflammation. The results also suggest that the inhibition of PGI(2) synthesis by NSAIDs and COX-2 inhibitors, in addition to that of PGE(2), contributes to their efficacy in treating the signs of arthritis.

Topics: Animals; Arthritis, Experimental; Carrageenan; Chromatography, High Pressure Liquid; Chronic Disease; Collagen; Cyclooxygenase 2 Inhibitors; Edema; Epoprostenol; Hot Temperature; Hyperalgesia; Inflammation; Iodoacetates; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoarthritis; Ovalbumin; Pain; Prostaglandins I; Rats; Rats, Sprague-Dawley; Receptors, Epoprostenol

A mixture of fatty acids obtained from sugar cane wax oil, the main components of which are palmitic, oleic, linoleic and linolenic acids, was evaluated topically in two experimental models of hypersensitivity: the ear swelling response to ovalbumin in sensitized mice (ED50 edema: 0.63 +/- 0.06 mg/ear, ED50 myeloperoxidase: 0.56 +/- 0.04 mg/ear, ED50 degranulated cells: 0.70 +/- 0,08 mg/ear) and oxazolone-induced contact hypersensitivity in mice (ED50 edema: 1.63 +/- 0.26 mg/ear, ED50 myeloperoxidase: 1.50 +/- 0.28 mg/ear, ED50 degranulated cells: 1.69 +/- 0.08 mg/ear). Also, the effect of this mixture was studied on the chemotaxis induced by fmlp (ED50: 25 +/- 3 microg/mL). The mixture showed anti-inflammatory activity in both in vivo models of allergy and in the chemotaxis test. Therefore, these results provide evidence about the potential usefulness of the mixture of fatty acids from sugar cane wax oil in cutaneous inflammatory and allergic disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Edema; Female; Hypersensitivity, Immediate; Mice; Mice, Inbred BALB C; Ovalbumin; Oxazolone; Phytotherapy; Plant Oils; Saccharum

To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats.. Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control.. At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine.. In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.

Topics: Anaphylaxis; Animals; Capillary Permeability; Conjunctivitis, Allergic; Dibenzoxepins; Disease Models, Animal; Edema; Eyelids; Guinea Pigs; Histamine H1 Antagonists; Ketotifen; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Ovalbumin; Piperidines; Rats

We investigated the anti-allergic and analgesic properties of an oil and a derived fraction of tetranortriterpenoids (TNTP) obtained from the seeds of Carapa guianensis Aublet.. Pleurisy, paw and ear edema were induced in Swiss and C57/Bl10 mice mice, whereas thermal hyperalgesia was assessed in Wistar rats (n = 6-10 per group). Values of p < 0.05 were regarded as significant.. C. guianensis oil (100 to 400 mg/kg, p.o.) and TNTP (12.5 to 100 mg/kg, p.o.) inhibited pleural exudation, paw and ear edema induced by ovalbumin (OVA) in sensitized mice. TNTP (12.5 to 100 mg/kg, p.o.) also inhibited paw edema induced by histamine, PAF and bradykinin. TNTP (100 mg/kg, p.o.) inhibited prostaglandin E(2) generation in the pleural cavity in response to antigenic challenge. Moreover, C. guianensis oil (100 to 400 mg/kg) and TNTP (12.5 to 100 mg/kg) decreased OVA- and histamine-induced hyperalgesia.. Taken together, these findings demonstrate the anti-edematogenic and analgesic effects of C. guianensis oil, and points out TNTP as the responsible bioactive compounds.

Topics: Allergens; Animals; Anti-Allergic Agents; Bradykinin; Capillary Permeability; Dinoprostone; Dose-Response Relationship, Drug; Edema; Histamine; Hyperalgesia; Inflammation; Limonins; Meliaceae; Mice; Mice, Inbred C57BL; Models, Chemical; Ovalbumin; Permeability; Plant Extracts; Rats; Rats, Wistar

We studied the effect of rolipram, a phosphodiesterase (PDE) IV inhibitor, on allergic footpad swelling in mice. For this study, varying adjuvants including complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and Imject Alum (Alum) were used because the extent of antigen-specifically induced T helper type 1 (Th1) and Th2 responses had been shown to depend on adjuvants used. To induce allergic footpad swelling, we immunized mice with ovalbumin (OVA) emulsified in either CFA or IFA, dissolved in Alum or in phosphate-buffered saline (PBS) as a control (day 0), followed by subcutaneous injection of the antigen into footpads on day 21. Rolipram was given orally to the animals daily from days 0-20. Results showed that treatment with rolipram was followed by an increase in early swelling at 0.5 h and a decrease in late swelling at 6 and 24 h in the CFA group. In the IFA group, rolipram significantly enhanced swelling at, but not after, 30 min. In the Alum and the PBS groups, the PDE inhibitor failed to affect the OVA-specific footpad reaction at all times examined. Treatment of the CFA and IFA groups with rolipram significantly inhibited the production of the Th1 antibody anti-OVA immunoglobulin G2a (IgG2a), and the drug enhanced Th2 cell-dependent anti-OVA IgE production. In both groups, rolipram also enhanced the secretion of Th2 cytokines including interleukin-4 (IL-4) and IL-10. These findings suggest that rolipram may facilitate early allergic footpad swelling mediated by Th2 immune responses, while the late phase of swelling associated with Th1 responses may be attenuated by the PDE IV inhibitor.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adjuvants, Immunologic; Animals; Cells, Cultured; Cyclic Nucleotide Phosphodiesterases, Type 4; Edema; Foot; Hypersensitivity; Male; Mice; Mice, Inbred DBA; Ovalbumin; Phosphodiesterase Inhibitors; Rolipram; Spleen; Th1 Cells; Th2 Cells

Food allergy is an important and common health issue, and there is a need to identify and characterize the sensitizing mechanisms. One of the common causes of food allergy is ovalbumin (OVA), a dietary antigen from eggs. We hypothesized that OVA-induced food allergy in the gut involves the activation of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES), which then recruits eosinophils to lesioned tissue. The purpose of this study was to clarify whether RANTES expression correlates with eosinophil infiltration in the gut of OVA-sensitized BALB/c mice in response to oral OVA challenge. BALB/c mice were immunized with OVA 1 microg and sensitized after 2 weeks by intragastric administration of OVA. Sensitization to the oral OVA challenge was analyzed by examining eosinophil infiltration into the gut tissue (immunohistochemistry), mucosal eosinophil cationic protein (ECP) concentration, and RANTES mRNA expression (reverse-transcriptase polymerase chain reaction and Southern blotting) at 3, 6, 12, and 24 h after the challenge. There was marked edema of the intestinal villi, and eosinophil infiltration to the lamina propria peaked at 6 h in OVA-sensitized mice. RANTES mRNA expression peaked at 3 h and 6 h and declined thereafter. The expression of RANTES mRNA in the allergic mice was much higher than in the nonallergic, normal, or unsensitized control mice. Tissue eosinophilia and intestinal ECP levels were significantly correlated with the RANTES mRNA level. We conclude that RANTES may play a central role in the pathogenesis of food-mediated gastrointestinal allergy.

Topics: Animals; Chemokine CCL5; Disease Models, Animal; Edema; Eggs; Eosinophils; Female; Food Hypersensitivity; Immunoglobulin E; Intestinal Mucosa; Jejunum; Leukocyte Count; Mice; Mice, Inbred BALB C; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

In the present study, we investigated the participation of chemical mediators in the development of experimental allergic conjunctivitis in rats. Cetirizine (a histamine H1 receptor antagonist), ramatroban (a thromboxane A2 (TXA2) receptor antagonist) and zafirlukast (a cysteinyl leukotrienes (cys-LTs) receptor antagonist) were orally administered from day 14 to day 42 during repeated topical antigen challenge. An increase in reactivity to antigen- and histamine-induced eye scratching behavior was observed by topical sensitization in sensitized rats. Although increased reactivity to antigen was not influenced by cetirizine, ramatoroban and zafirlukast, increased reactivity to histamine was significantly inhibited by ramatroban. The development of conjunctival edema was also observed for topical sensitization. Cetirizine caused no inhibition of the development of conjunctival edema, but ramatroban and zafirlukast inhibited the development of conjunctival edema. In addition, the number of eosinophils in the conjunctiva was increased by topical sensitization. Cetirizine had no significant effect on the increase in the number of eosinophils. However, ramatroban and zafirlukast were effective in inhibiting an increase in the number of eosinophils induced by topical sensitization. These results indicate that TXA2 is involved in increased histamine reactivity, and TXA2 and cys-LTs are associated with not only the conjunctival edema but also eosinophil infiltration during the development of experimental allergic conjunctivitis in rats.

Topics: Administration, Oral; Animals; Carbazoles; Cetirizine; Conjunctivitis, Allergic; Disease Models, Animal; Edema; Eosinophilia; Histamine H2 Antagonists; Indoles; Leukotriene Antagonists; Male; Membrane Proteins; Ovalbumin; Phenylcarbamates; Pruritus; Rats; Rats, Wistar; Receptors, Histamine H2; Receptors, Leukotriene; Receptors, Thromboxane A2, Prostaglandin H2; Sulfonamides; Tosyl Compounds

The murine model of ovalbumin (OVA)-induced allergy was used to evaluate the effectiveness of oral treatment with the leaf extract of Cissampelos sympodialis Eichl. (Menispermaceae) (CS) in the modulation of immunoglobulin E (IgE) production and T cell activation. CS treatment with doses ranging from 200 to 600 mg/Kg/day for 15 days before and during OVA-sensitization promoted reduction in total and OVA-specific serum IgE. CS at 400 or 600 mg/Kg/day also reduced paw edema induced by local OVA challenge. Daily intake of up to 600 mg/Kg of oral CS by BALB/c mice did not reduce weight gain, which is indicative of a lack of systemic toxicity. To assess the effect of CS treatment on T cell proliferative response to stimuli in vitro, the mitogenic response of spleen cells of treated and control animals were evaluated. Cells from CS-treated animals showed an elevated background proliferative response to concanavalin-A (Con-A) when compared to those from control animals. Oral intake of CS increased the in vitro production of IFN-gamma and IL-10 by Con-A stimulated cells. Mice treated with 200 mg/Kg/day CS showed increasing levels of IFN-gamma. These results show that oral treatment with Cissampelos sympodialis extract has an immunomodulatory effect, reducing allergy-associated responses possibly by a preferential activation of Th1-type cytokines.

Topics: Administration, Oral; Animals; Cissampelos; Cytokines; Edema; Female; Immunoglobulin E; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Th1 Cells

We tested the hypothesis whether allergic airway inflammation in ovalbumin sensitized and challenged Brown Norway rats is associated with intrinsic surfactant alteration and dysfunction. The determination of intra-alveolar surfactant subtypes and alveolar edema within their original microenvironment is only possible using an ultrastructural stereological approach. Therefore both lungs of control and asthmatic rats were fixed by vascular perfusion. The volume fractions of surfactant subtypes and the epithelial surface fraction covered with alveolar edema were determined by point and intersection counting. Furthermore, lung resistance was measured by means of whole-body plethysmography. The surface activity of surfactant from bronchoalveolar lavage was determined as minimum surface tension at minimal bubble size with a pulsating bubble surfactometer. Compared with controls, in asthmatics (1) the fraction of inactive unilamellar forms was significantly increased from 56% to 66%, (2) the fraction of alveolar epithelium covered with alveolar edema visible by light microscopy was significantly increased from 0.7% to 5.0%, (3) the fraction of alveolar epithelium covered with fluid seen by electron microscopy expanded significantly from 5% to 21%, (4) lung resistance was significantly elevated from 14% to 86% and (5) surface tension was enhanced from 6 mN/m to 12 mN/m. Thus, the inflammatory process after allergen challenge of sensitized Brown Norway rats causes intra-alveolar surfactant alterations. These surfactant alterations might contribute to small airway dysfunction.

Topics: Administration, Inhalation; Aerosols; Animals; Asthma; Blood-Air Barrier; Disease Models, Animal; Edema; Immunization; Injections, Subcutaneous; Lung; Male; Ovalbumin; Pulmonary Alveoli; Pulmonary Surfactants; Rats; Rats, Inbred BN; Respiratory Function Tests

Recognition of foreign substances by innate immunity through pattern recognition receptors (PRRs) regulates acquired immunity such as allergic reaction. Because PRRs recognize heterogeneous ligands, daily food intake can potentially regulate immune allergic reaction.. Elucidation of the effect of lambda-carrageenan on allergic reactions was aimed.. IFN-gamma and IL-4 was measured in in vitro T cell-stimulated culture. Cytokine production from macrophages in response to lambda-carrageenan was measured as indicator for innate immunity activation. Mice were immunized with OVA in alum to induce specific IgE, and then histamine release was induced by systemic injection of OVA.. Activation of innate immunity by lambda-carrageenan is dependent on Toll-like receptor-4 (TLR4) and MyD88, in which induction of pro-inflammatory cytokines such as TNF-alpha and IL-6 was largely impaired in macrophages from TLR4- and MyD88-deficient mice. Footpad oedema, a model for in vivo inflammatory reactions, was significantly reduced in these mice. Similar to recent evidence showing a preference for the stimulation of Th1 via TLR/MyD88 signalling, lambda-carrageenan showed enhanced IFN-gamma and decreased IL-4 in stimulated T cell cultures. Interestingly, increased IFN-gamma production was still seen in TLR4- and MyD88-deficient splenocytes. Oral administration of lambda-carrageenan to immunized mice successfully decreased OVA-specific IgE, and lambda-carrageenan was also effective in previously immunized mice. Further, serum histamine release upon systemic challenge of OVA was significantly inhibited. Neither OVA-specific IgG1/IgG2a nor cytokine secretion from in vitro cultures were altered, suggesting the involvement of multiple PRRs as demonstrated by TLR4/MyD88-independent IFN-gamma up-regulation. The simultaneous feeding of OVA with lipopolysaccharide abrogated oral tolerance, but lambda-carrageenan was not only devoid of such an effect but was also found to promote oral tolerance in the absence of TLR4.. lambda-Carrageenan was suggested to be a useful dietary supplement to ameliorate allergic reactions while maintaining oral tolerance-dependent intestinal homeostasis.

Topics: Adaptor Proteins, Signal Transducing; Administration, Oral; Animals; Antigens, Differentiation; Carrageenan; Cells, Cultured; Drosophila Proteins; Edema; Female; Histamine Release; Hypersensitivity; Immune Tolerance; Immunoglobulin E; Interferon-gamma; Interleukin-4; Macrophage Activation; Membrane Glycoproteins; Mice; Mice, Inbred Strains; Mitogens; Myeloid Differentiation Factor 88; Ovalbumin; Receptors, Cell Surface; Receptors, Immunologic; Spleen; Th1 Cells; Th2 Cells; Toll-Like Receptor 4; Toll-Like Receptors

We investigated the effects of 1-4% ointments of metronidazole and tinidazole (derivatives of nitroimidazole) on models of inflammatory dermatitis evoked by antigen, hapten and monoclonal anti-dinitrophenol (DNP) IgE antibody in mice. Metronidazole and tinidazole ointments (1) suppressed the late-phase reaction (LPR) of biphasic ear edema in mice sensitized with ovalbumin (OA), (2) suppressed trinitrochlorobenzene-induced inflammatory dermatitis, (3) suppressed the immediate phase reactions and LPR in mice passively sensitized with anti-DNP IgE mAb, and (4) enhanced vascular permeability and the number of scratching reactions, presumably due to itching, in passively sensitized mice. These results strongly indicate that metronidazole and tinidazole 1-4% ointments possess antiinflammatory, immunosuppressive and anti-itching effects, and have the potential for clinical use in the treatment of human inflammatory skin diseases including atopic dermatitis in addition to rosacea and acne vulgaris.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Antipruritics; Capillary Permeability; Dermatitis; Dermatologic Agents; Disease Models, Animal; Edema; Humans; Immunosuppressive Agents; Male; Metronidazole; Mice; Ointments; Ovalbumin; Picryl Chloride; Pruritus; Tacrolimus; Tinidazole

This study was designed to evaluate the anti-inflammatory effect of Sclerocarya birrea (family: Anacardiaceae) stem-bark aqueous and methanolic extracts in rats. Young adult, male Wistar rats (Rattus norvegicus) weighing 250-300g were used. The anti-inflammatory effects of aqueous and methanolic stem-bark extracts of the plant (SB, 500mg/kg p.o.) were examined on rat paw oedema induced by subplantar injections of fresh egg albumin (0.5ml/kg). Acetylsalicylic acid (ASA, 100mg/kg p.o.) was used as the reference anti-inflammatory agent for comparison. Both the aqueous and methanolic stem-bark extracts of S. birrea (SB, 500mg/kg p.o.) progressively and time-dependently reduced rat paw oedema induced by subplantar injections of fresh egg albumin. However, the methanolic extract of the plant produced relatively greater and more pronounced anti-inflammatory effect than its aqueous extract counterpart in the experimental animal model used. The two extracts of S. birrea stem-bark were found to be markedly less potent than ASA as anti-inflammatory agent. Although both the aqueous and methanolic extracts of S. birrea stem-bark are less potent than ASA as anti-inflammatory agent, the results of this experimental animal study indicate that the extracts possess anti-inflammatory activity, and thus lend credence to the suggested folkloric use of the plant in the management and/or control of arthritis and other inflammatory conditions in certain communities of South Africa.

Topics: Anacardiaceae; Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Lethal Dose 50; Male; Medicine, African Traditional; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Bark; Plant Extracts; Plant Stems; Rats; Rats, Wistar

Sphaeranthus senegalensis Vaill (Asteraceae) is used in traditional medicine as a remedy for rheumatic pains and other ailments. The anti-inflammatory and anti-nociceptive activity of the aqueous extract of the whole shoot of the plant was evaluated in mice and rats. Activity of the extract against egg-albumin induced hind paw oedema was measured to evaluate the anti-inflammatory activity while the anti-nociceptive potency was evaluated using three painful stimuli viz acetic acid induced abdominal constriction and hot plate test in mice, and the formalin test in rats. Results indicated that the extract possess remarkable dose dependent anti-inflammatory activities in rats. The extract also showed anti-nociceptive activities against acetic acid induced writhing, formalin and the hot plate pain models. The effects were significant (P < 0.05) when compared with the saline control group. The results suggest the presence of a potent anti-inflammatory and anti-nociceptive principle in the extract, which support the folkloric use of the plant in relieving rheumatic pains.

Topics: Acetates; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asteraceae; Edema; Female; Formaldehyde; Hot Temperature; Male; Mice; Nigeria; Ovalbumin; Pain Measurement; Rats; Rats, Wistar

Rats are commonly used in anaphylaxis models, mainly in intestinal anaphylaxis. Hypersensitivity mechanisms are complex and they are not clearly defined. Ovalbumin (OVA) is commonly used for studies on the hypersensitivity mechanism. However, the potential pro-inflammatory mediators induced by this antigen in the model of paw oedema in immunized rats are still not completely understood. This work examines the pharmacological modulation of several mediators involved in rat hind paw immune oedema induced by OVA. Wistar rats were previously immunized (14-18 days) with OVA (30 microg, intraperitoneally) or sham-sensitized with aluminum hydroxide (control). The paw volumes were measured before the antigenic stimuli and 1, 2, 3 and 4 h after the intraplantar injection of OVA (10 microg/paw). Subcutaneous injection of dexamethasone, diphenhydramine, cyproheptadine, chlorpromazine or methysergide significantly inhibited (p < 0.05) the allergic paw oedema. The dual inhibitor of cyclooxygenase and lipoxygenase (NDGA), the cyclooxygenase inhibitor (indomethacin), the lipoxygenase inhibitor (MK-886), the PAF antagonist (WEB 2086), the mast cell stabilizer (ketotifen), and the anti-histamine (meclizine) did not inhibit the immune oedema. In addition, thalidomide and pentoxifylline (anti-tumour necrosis factor drugs) were ineffective against OVA-induced oedema. The fact that indomethacin, MK-886, NDGA and WEB 2086 are unable to inhibit this allergic oedema indicates that the dexamethasone action seems not to be via phospholipase A2, but possibly due to the synthesis and/or the inhibitory activity of cytokines. The paw oedema inhibition by diphenhydramine, but not by meclizine, may suggest a different mechanism, which is independent of the effect of histamine. These data indicate that allergic oedema is more sensitive to anti-serotonin drugs, mainly anti-5-HT2, suggesting that the principal mediator of this inflammatory response is serotonin.

Topics: Animals; Anti-Allergic Agents; Azepines; Chlorpromazine; Dopamine Antagonists; Dose-Response Relationship, Immunologic; Edema; Enzyme Inhibitors; Foot; Histamine H1 Antagonists; Hypersensitivity; Immunization; Immunosuppressive Agents; Ketotifen; Ovalbumin; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Triazoles

The effects of aqueous and methanolic extracts of Hypoxis hemerocallidea corm, locally known as 'African potato' in South Africa, were examined on rat paw edema induced by subplantar injections of fresh egg albumin (0.5 ml/kg). Acetyl salicylic acid (100 mg/kg p.o.) was used as the reference antiinflammatory agent for comparison. Both the aqueous and methanolic extracts of H. hemerocallidea corm (500 mg/kg p.o.) progressively reduced rat paw edema induced by the subplantar injections of fresh egg albumin. The methanolic extract produced relatively greater and more pronounced antiinflammatory effect than the aqueous extract in the experimental animal model used. However, the two extracts of African potato examined in this study were found to be less potent than acetyl salicylic acid (ASA) as an antiinflammatory agent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Administration Schedule; Edema; Female; Hindlimb; Hypoxis; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Solanum tuberosum; South Africa

The influence of stress and diazepam treatment on airway inflammation was investigated in ovalbumin (OVA)-sensitized rats. Animals were injected with OVA plus aluminum hydroxide intraperitoneally (day 0) and boosted with OVA subcutaneously (day 7). From the first to 13th day after sensitization, rats were treated with diazepam, and 1 h later they were placed in a shuttle box where they received 50 mild escapable foot shocks/day preceded by a sound signal (S). Response during the warning (S) canceled shock delivery and terminated the S. On day 14, rats were submitted to a single session of 50 inescapable foot shocks preceded by S and then were challenged with OVA. High levels of stress were detected in shocked animals, manifested as ultrasonic vocalizations. Morphometric analysis of stressed animals revealed a significant increase in both edema and lymphomononucleated cells in airways compared with controls. Diazepam treatment reduced edema in stressed and nonstressed rats. No differences were found in polymorphonucleated cell infiltration. Diazepam treatment reduced lymphomononucleated cell infiltration in stressed animals. These data suggest that stress and diazepam treatment play relevant roles in edema and lymphomononucleated airway inflammation in OVA-sensitized rats.

Topics: Administration, Inhalation; Anaphylaxis; Animals; Anti-Anxiety Agents; Bronchial Diseases; Conditioning, Psychological; Diazepam; Edema; Electroshock; Injections, Intraperitoneal; Lung; Male; Ovalbumin; Pneumonia; Rats; Rats, Wistar; Specific Pathogen-Free Organisms; Stress, Physiological

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcstraightepsilonRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.

Topics: Anaphylaxis; Animals; Antigens, Surface; Edema; Female; Male; Mast Cells; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin; Passive Cutaneous Anaphylaxis; Receptors, Immunologic

Late phase allergic response has been implicated in the pathogenesis of allergic diseases. In the current study, we investigated the role of IL-4, IL-5 and mast cells in the development of cutaneous late phase reaction (LPR) in mice. Antigenic challenge of ears of ovalbumin (OVA)-immunized BALB/c mice caused a biphasic ear swelling peaking at 1 hr (immediate phase reaction; IPR) and 24 hr (LPR). Ear swelling in LPR was significantly suppressed by the treatment with anti-IL-4 monoclonal antibody (mAb) before antigen challenge. Local eosinophil accumulation during LPR, however, was not inhibited by anti-IL-4 mAb. Moreover, anti-IL-5 mAb had no effect on the swelling response though it significantly suppressed the local accumulation of eosinophils. Interestingly, mast cell-deficient mice (WBB6F1-W/Wv) developed LPR without exhibiting IPR, while the magnitude of ear swelling and local eosinophilia was significantly lower than in normal congenic mice (+/+ mice). The present findings show that IL-4 and IL-5 differently regulate the development of LPR, and that IgE-mediated mast cell activation is required for full response.

Topics: Animals; Antibodies, Monoclonal; Cell Movement; Dermatitis, Allergic Contact; Ear, External; Edema; Eosinophils; Hypersensitivity, Delayed; Immunoglobulin E; Interleukin-4; Interleukin-5; Male; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Knockout; Ovalbumin

Because interferon-gamma, interleukin-4, and interleukin-5 have been identified at the mRNA and protein levels in the lesional skin of patients with atopic dermatitis, we investigated the roles played by granulocytes as effector cells in allergic inflammation by using two unique murine skin models. In vitro generated Th1 and Th2 cells from naïve splenocytes of antiovalbumin T cell receptor transgenic BALB/C mice were adoptively transferred with ovalbumin into the ear pinnae or air-pouches produced in the back skin of naïve, nontransgenic BALB/C mice. The injection of Th1 cells with ovalbumin induced delayed type ear swelling that peaked at 48 h, whereas that of Th2 resulted in ear swelling that peaked at a much earlier time, 24 h. Histologic study of the swollen ear skin and granulocytes recruited into the air-pouch demonstrated that, although the Th1-induced inflammation caused a neutrophil-predominant infiltrate with few eosinophils, larger numbers of eosinophils accumulated in the Th2-induced inflammation. Using these murine models, we further evaluated the effects of drugs used for the treatment of atopic diseases. The results showed that FK506 administration could effectively reduce skin inflammation induced by either Th cells. Interestingly, the neutrophil elastase inhibitor ONO-6818 efficiently inhibited Th1-induced inflammation. In contrast, a leukotriene receptor antagonist, ONO-1078, specifically suppressed Th2-induced inflammation. We also found that each ONO drug exerted direct influence on specified granulocytes, as neither affected in vitro production of relevant Th cytokines. Thus, we succeeded in developing animal skin inflammation models in which we can evaluate the contribution of protein antigen-specific Th1 or Th2 cells through the action of granulocytic effector cells.

Topics: Animals; Cells, Cultured; Chromones; Dermatitis, Atopic; Disease Models, Animal; Ear; Edema; Enzyme Inhibitors; Eosinophils; Hypersensitivity; Immunosuppressive Agents; Leukotriene Antagonists; Male; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Oxadiazoles; Pyrimidinones; Skin; Tacrolimus; Th1 Cells; Th2 Cells

This study evaluates further the anti-inflammatory and anti-allergic properties of polygodial, a sesquiterpene extracted from the barks plant Drymis winteri (Winteraceae). Polygodial (12.8-128.1 micromol/kg, i.p.) 30 min prior, inhibited significantly the mouse paw oedema induced by prostaglandin E2, bradykinin (BK) substance P (SP), dextran, platelet activating factor (PAF) or carrageenan. Polygodial also inhibited arachidonic acid-, capsaicin- and croton oil-induced ear oedema in mice. Polygodial (42.7 micromol/kg, i.p.), significantly inhibited both exudation and cell influx when assessed in the pleurisy induced by SP and histamine, and to a less extent the inflammatory response caused by carrageenan, PAF, BK and des-Arg9-BK. Finally, polygodial (4.2-42.7 micromol/kg, i.p.) produced dose-related inhibition of paw oedema induced by ovalbumin, protecting in a time-dependent manner the anaphylactic shock induced by endovenous administration of ovalbumin in animals which had been actively sensitised by this antigen. These and our previous results indicate that the major component present in the bark of the plant D. winteri, the sesquiterpene polygodial exerts an interesting anti-inflammatory and anti-allergic properties when assessed in rats and mice.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Hindlimb; Inflammation Mediators; Male; Mice; Ovalbumin; Pleurisy; Rats; Rats, Wistar; Sesquiterpenes

Effects of 3,5-dimethoxy-4-hydroxybenzoic acid and 2,3,4-trihydroxyacetophenone were studied on haemoglobin S (Hb S) polymerisation, analgesia and inflammation using Hb S solution, rats and mice. UV spectrophotometric procedure was used to monitor the polymerization of the Hb S. Acetic acid induced writhing in mice and egg albumin induced rat paw edema procedures were used to evaluate analgesic and anti-inflammatory activities of the compounds respectively. The results indicate that both drugs inhibit the process of polymerization significantly, possibly by direct action on the Hb S molecules. The drugs inhibited acetic acid induced pain and decreased egg albumin induced oedema. It is concluded that 3,5-dimethoxy-4-hydroxybenzoic acid and 2,3,4-trihydroxyacetophenone may have some value in the management of sickle cell disease.

Topics: Acetic Acid; Acetophenones; Analgesics; Anemia, Sickle Cell; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antisickling Agents; Edema; Female; Guinea Pigs; Hemoglobin, Sickle; Humans; Hydroxybenzoates; Lethal Dose 50; Male; Mice; Ovalbumin; Pain; Rabbits; Rats; Rats, Wistar

Selectins play an important role on leukocytes infiltration into inflammatory tissues. To understand the role of selectins, we investigated the effects of selectin-IgG chimeras and anti selectin antibodies on the murine IgE-mediated skin inflammation model. Biphasic skin reactions were induced by intradermal challenge with ovalbumin (OA) to ears of actively sensitized mice. This reaction was characterized by immediate and late phase responses observed as which were induced via a rapid increase in capillary permeability and leukocyte infiltration, respectively. The expression of E-selectin mRNA was significantly increased to reach its highest level at 2 h after OA challenge. E-, P-, and L-selectin-IgG chimeras inhibited the late phase responses, i.e. ear swelling, neutrophil infiltration and eosinophil infiltration at 24 h after OA challenge in a dose-dependent manner at dose range of 0.1 - 10 mg kg(-1), i.v. Antiselectin antibodies did not inhibit the increase of ear swelling. But anti E- and P-selectin antibodies significantly inhibited neutrophil infiltration and eosinophil infiltration. These results indicate that selectins play an important role on the late phase response of the murine IgE-mediated skin inflammation model by mediating inflammatory cell adhesion to endothelium.

Topics: Animals; Antibodies, Monoclonal; Dose-Response Relationship, Drug; E-Selectin; Ear; Edema; Eosinophil Peroxidase; Female; Gene Expression Regulation; Hypersensitivity, Delayed; Immunoglobulin E; Immunoglobulin G; Inflammation; Injections, Subcutaneous; L-Selectin; Mice; Mice, Inbred BALB C; Ovalbumin; P-Selectin; Peroxidase; Peroxidases; Recombinant Fusion Proteins; RNA, Messenger; Selectins; Skin; Time Factors

A number of studies demonstrating the important role of interleukin-5 (IL-5) in eosinophil infiltration were reported. Antigen-induced eosinophil infiltrations to the trachea and skin were inhibited by pretreatment with monoclonal anti-IL-5 antibody. In this study, the role of IL-5 in eosinophil infiltration to the gut by oral challenge in mice is investigated. A marked eosinophil infiltration to the lamina propria was induced by oral challenge with ovalubumin (OVA) in Balb/c mice intraperitoneally sensitized with OVA, and peaked at 6 h after the oral challenge. Intraperitoneal preadministration of monoclonal anti-IL-5 antibody significantly decreased the eosinophil infiltration to the lamina propria. Furthermore, analysis by reverse transcription polymerase chain reaction (RT-PCR) demonstrated that IL-5 mRNA expression was induced in the lamina propria in an antigen-specific manner and the expression peaked at 6 h and declined thereafter. In-situ hybridization (ISH) revealed the presence of IL-5 mRNA positive cells at lesion site. As in bronchial mucosa and skin, IL-5 may play an important role in eosinophil recruitment to the lesion site in IgE mediated gut late phase reaction.

Topics: Animals; Antibodies, Monoclonal; Cell Movement; Chemotactic Factors, Eosinophil; Edema; Eosinophils; Female; Food Hypersensitivity; In Situ Hybridization; Interleukin-5; Intestinal Mucosa; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

We assessed the effects of neurokinin (tachykinin) depletion by capsaicin (CAP) treatment on airway inflammation induced by repeated ovalbumin (OA) aerosol exposures (twice a week for 4 wk) in guinea pigs. The animals were then anesthetized, tracheostomized, mechanically ventilated and challenged with ovalbumin aerosol. Maximal values of respiratory system resistance and elastance after antigen challenge were significantly lower in capsaicin-treated guinea pigs than in intact animals (p < 0.001). Morphometric analysis of noncartilaginous airways revealed less intense bronchoconstriction (p < 0.001) and peribronchiolar edema (p < 0.001) in capsaicin-treated guinea pigs. Chronic antigen exposure resulted in a significant increase in lymphocytes and eosinophils both in bronchoalveolar lavage (BAL) fluid and airway wall. Immunohistochemistry with monoclonal antibodies revealed that most of the lymphocytes present in airway wall were CD4+ T cells. Capsaicin treatment resulted in values of CD4+ T cells in airway wall significantly lower than non-capsaicin-treated guinea pigs (p < 0.005). This difference was not observed in eosinophil recruitment. Our results suggest that neurokinin release by sensory nerve terminals results in an amplification of the pulmonary inflammatory changes induced by chronic antigen exposure. In addition, neurokinins play a role in T-cell recruitment induced by chronic allergen exposure.

Topics: Administration, Inhalation; Aerosols; Airway Resistance; Animals; Antigens; Bronchi; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Capsaicin; CD4 Lymphocyte Count; Edema; Elasticity; Guinea Pigs; Inflammation; Lung; Lung Compliance; Male; Ovalbumin; Tachykinins

We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex-mediated peritonitis and skin injury.

Topics: Animals; Antibodies; Antigens, CD; Arthus Reaction; Capillary Permeability; Cell Count; Complement System Proteins; Edema; Gene Targeting; Immune Complex Diseases; Immunoglobulin G; Inflammation; Interleukin-6; Lung; Mice; Mice, Knockout; Neutrophils; Ovalbumin; Peritonitis; Peroxidase; Receptor, Anaphylatoxin C5a; Receptors, Complement; Receptors, Fc; Tumor Necrosis Factor-alpha

This paper reports the anti-inflammatory effects of superoxide dismutase (SOD) from pig blood on inflammatory animal models. The experimental results have shown that SOD has significant anti-inflammatory effects. It inhibited carrageenin-induced foot-edema and croton oil induced granulation tissue edema of rats. It also inhibited arthritis induced by egg serum and Freund's adjuvant in rats. The effects were significantly dose-dependent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Croton Oil; Edema; Foot Diseases; Freund's Adjuvant; Male; Ovalbumin; Rats; Rats, Wistar; Superoxide Dismutase

The role of nitric oxide in allergic conjunctivitis was studied in a guinea pig model. The eyes of sensitized guinea pigs were challenged with ovalbumin (20 micrograms per eye) or histamine (20 micrograms per eye). Synthesis of nitric oxide (NO) was inhibited using L-NAME (200 micrograms per eye) or aminoguanidine (200 micrograms per eye). The formation of conjunctival edema was graded and levels of nitrite, a breakdown product of nitric oxide were measured in lavage fluid. Conjunctival vasopermeability was determined by measuring the albumin concentration in the fluid on the surface of the eye (lavage fluid). Animals were treated with sodium nitroprusside (SNP) or phenylephrine after which histamine induced conjunctival vasopermeability changes were measured. Drugs were administered topically with the other eye serving as a control. Both ovalbumin and histamine produced a marked inflammatory response including hyperaemia and edema. At the top of the inflammatory response occurring 30 min after challenge, increased levels of nitrite, a breakdown product of NO, were measured in lavage fluid. Prophylactic treatment with L-NAME or aminoguanidine resulted in a significant inhibition of the NO synthesis. Both L-NAME and aminoguanidine decreased conjunctival vascular permeability and edema formation significantly. Administration of SNP resulted in a marked dilatation of conjunctival blood vessels and produced a dose-dependent increase of vascular permeability. Addition of SNP to histamine significantly enhanced conjunctival edema and potentiated vascular permeability. These results indicate that NO is produced in the acute phase of allergic conjunctivitis and mediates vasodilatation after topical provocation with ovalbumin or histamine in sensitized guinea pigs. The resulting increase of the conjunctival blood flow subsequently increases the vascular permeability and enhances conjunctival edema formation. Inhibition of NO synthesis leads to a reduction of conjunctival hyperaemia and subsequently reduces the formation of edema.

Topics: Animals; Arginine; Capillary Permeability; Conjunctival Diseases; Conjunctivitis, Allergic; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Female; Guanidines; Guinea Pigs; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitroprusside; Ovalbumin; Phenylephrine

The uterine milk proteins (UTMP) are a pair of related glycoproteins that are the major secretory products of the endometrium of the pregnant ewe. UTMP are members of the serpin superfamily of serine protease inhibitors but have no known antiprotease activity. One possible role for UTMP is to inhibit uterine immune responses--UTMP inhibit mitogen and mixed lymphocyte-induced proliferation of peripheral blood lymphocytes, natural killer (NK) cell activity and abortion caused by NK cell activation. Present objectives were to further evaluate the lymphocyte-inhibitory activity of UTMP and test whether UTMP modify immune responses in vivo.. One experiment demonstrated that UTMP inhibited antigen-induced lymphocyte proliferation induced by Candida albicans extract. In another experiment, ewes were immunized with OVA mixed with 3.75 mg/ml of UTMP or ovine serum albumin (OSA control). Injections of 1 mg OVA+UTMP or OSA in incomplete adjuvant were administered 6 wk later. Titers of antibody to OVA were lower (P < 0.001) for ewes administered UTMP than for ewes administered OSA. Effects of UTMP on delayed hypersensitivity reactions were evaluated in three experiments using skin-fold thickness assays.. UTMP did not inhibit the increase in skin-fold thickness caused by PHA and Mycobacterium tuberculosis but rather tended to increase the response to PHA.. Results strengthen the thesis that UTMP are physiologically relevant immunoregulatory molecules. Nonetheless, effects on skin-fold responses indicate that actions of UTMP can be more complex than would be predicted based on the proteins only having a single biological effect.

Topics: Animals; Antibody Formation; Antigens, Fungal; Cells, Cultured; Edema; Endometrium; Female; Glycoproteins; Hypersensitivity, Delayed; Immune Tolerance; Immunity, Cellular; Immunosuppressive Agents; Lymphocyte Activation; Mycobacterium tuberculosis; Ovalbumin; Phytohemagglutinins; Pregnancy; Progesterone; Serpins; Sheep; Skinfold Thickness

This study investigated the influence of the selective endothelin (ET) ETA receptor antagonists BQ-123 and FR 139317 on paw edema induced by ovalbumin (OVA) injection (3 micrograms/paw) to OVA-sensitized mice [50 micrograms in 5 mg of Al(OH)3, s.c., 14 days earlier]. Injections of BQ-123 (1.5, 15, and 150 pmol/paw, 15 min earlier) reduced OVA-induced edema from 59.6 +/- 4.0 to 48.3 +/- 5.4, 44.6 +/- 3.8, and 34 +/- 2.0 microliters, respectively (p < 0.05; n = 6). Like BQ-123, FR 139317 (7.5, 75, and 750 pmol/paw) also inhibited OVA-induced edema in a graded fashion but was less potent. In contrast, BQ-123 (150 pmol/paw) failed to affect paw edema induced in nonsensitized mice by histamine (100 micrograms/paw), serotonin (100 micrograms/paw), or zymosan (500 micrograms/paw), but significantly reduced edema induced by carrageenan (300 micrograms/paw) by 30% (p < 0.05). These results strongly suggest that endogenous ETs, acting through ETA receptors, play an important proinflammatory role in the allergic reaction to OVA.

Topics: Animals; Azepines; Edema; Endothelin Receptor Antagonists; Endothelins; Indoles; Male; Mice; Ovalbumin; Peptides, Cyclic; Receptor, Endothelin A

T cells play a dominant role in the pathogenesis of collagen-induced arthritis (CIA). The effector mechanism involves a delayed-type hypersensitivity reaction in the synovial joint. Here we describe a new test system, named a flare reaction, to monitor directly this inflammatory T cell function. It is shown that type II collagen (CII) injected into the pinna of the ear is a target for CII-reactive inflammatory T cells formed during the early pathogenesis of CIA. The inflammatory swelling of the joint and the CII-injected ear in CIA rats develop in a coordinated manner. This assay greatly facilitates monitoring of in vivo activated inflammatory T cells during the induction of CIA.

Topics: Animals; Arthritis, Experimental; Collagen; Ear, External; Edema; Hypersensitivity, Delayed; Immunization; Immunosuppression Therapy; Ovalbumin; Rats; Rats, Inbred Strains; T-Lymphocytes

1. In guinea-pigs previously sensitized with ovalbumin, the intra-plantar administration of the antigen induced dose-dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h). 2. Oedema induced by ovalbumin at the doses of 50 or 200 micrograms/paw was not inhibited by antihistamines (meclizine and cetirizine), a PAF antagonist (BN 50730), a cyclo-oxygenase inhibitor (indomethacin), a lipoxygenase inhibitor (MK-886), a dual type lipo- and cyclo-oxygenase inhibitor (NDGA), a bradykinin antagonist (Hoe 140) or the combination of cetirizine, MK-886, indomethacin and BN 50730. These drugs did inhibit paw oedema induced by their specific agonists or by carrageenin. These results suggest that histamine, PAF, prostaglandins, leukotrienes or bradykinin are not important in the development of immune paw oedema in guinea-pigs. 3. Dexamethasone (10 mg kg-1) inhibited oedema induced by ovalbumin (50 or 200 micrograms/paw, P < 0.05). This effect apparently does not result from inhibition of arachidonate metabolism, since indomethacin, MK-886 and NDGA were without effect. 4. Oedema induced by ovalbumin (50 or 200 micrograms/paw) was also inhibited by azelastine. This effect was not due to the anti-histaminic property of azelastine since two other potent-antihistamines, meclizine and cetirizine, were ineffective. 5. Intravenous injection of lipopolysaccharide (LPS) dose-dependently inhibited the oedema induced by ovalbumin (200 micrograms/paw). This effect could not be attributed to hypotension or leucopenia since the maximal dose applied (81 micrograms kg-1) did not induce significant changes in the blood pressure or in the white blood cell levels of the animals. It is suggested that the effect of LPS is mediated by the endogenous release of cytokines, including tumour necrosis factor (TNF alpha). Murine TNF alpha dose dependently(9-81 microg kg-1) inhibited the paw oedema induced by ovalbumin.7. The anti-oedematogenic effects of LPS and/or TNF alpha are possibly associated with their capacity to inhibit leucocyte emigration. Accordingly, guinea-pigs rendered leucopenic with vinblastine exhibited less intense oedema after ovalbumin. Vinblastine did not affect oedema induced by PAF or bradykinin,indicating that vascular responsiveness was not involved.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Dexamethasone; Edema; Enzyme-Linked Immunosorbent Assay; Foot; Guinea Pigs; Hypersensitivity; Immunoglobulin G; Leukocyte Count; Leukocytes; Leukopenia; Lipopolysaccharides; Male; Mice; Ovalbumin; Phthalazines; Platelet Aggregation Inhibitors; Tumor Necrosis Factor-alpha; Vinblastine

As a kind of anti-inflammatory protein fractionated and purified from the larva of parasa sinica, CCP (ip) has a significant anti-inflammatory effect on ear odema induced by croton oil in mice. Its ID50 is 1.6mg/kg, but a dose of 2.5mg/kg can also significantly inhibit the rat ankle odema induced by carrageenan and egg white.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Croton Oil; Edema; Female; Insect Hormones; Male; Materia Medica; Mice; Mice, Inbred C57BL; Moths; Ovalbumin; Rats; Rats, Sprague-Dawley

Endogenous glucocorticoids undoubtedly play a role in the control of immune responses: their contribution to inter-strain variation is unknown. The development of specific IgG and IgE was measured following inoculation with ovalbumin in Lewis, Fischer, Wistar and Brown Norway rats. The Lewis gives a smaller IgG and IgE response than the other strains and the response in vivo to antigen injected into the paw correlates with the titre of specific antibody. Treatment with the steroid receptor antagonist RU486 (mifepristone) following inoculation reveals that in the Lewis, and to a lesser extent in the Brown Norway, the development of a specific IgG response is limited by endogenous corticosteroids. The IgG response in different strains is differently sensitive to treatment with the synthetic glucocorticoid dexamethasone, the Lewis being particularly resistant. The importance of control by endogenous corticosteroids should not be overlooked in contributing to strain differences in immune response.

Topics: Adrenal Cortex Hormones; Animals; Antibody Specificity; Body Weight; Dexamethasone; Edema; Female; Freund's Adjuvant; Immunoglobulin E; Immunoglobulin G; Male; Mifepristone; Ovalbumin; Rats; Rats, Inbred BN; Rats, Inbred F344; Rats, Inbred Strains; Rats, Wistar; Species Specificity

The interference of the novel platelet-activating factor (PAF) receptor antagonist compound PCA 4248 with paw edema induced by antigen in sensitized boosted or unboosted mice was studied. Although PAF-induced edema was of similar intensity in non-sensitized and in both groups of sensitized mice, PCA 4248 was less effective in inhibiting paw edema induced by PAF in boosted mice. Paw edema induced by antigen in unboosted mice was refractory to PCA 4248 under conditions where edema in boosted mice was inhibited. Our results demonstrate that the PCA 4248 displays an anti-PAF activity in non-sensitized mice that is reduced by the booster injection of antigen. PAF plays an important role in the anaphylactic edema in boosted but not in unboosted mice.

Topics: Animals; Dihydropyridines; Edema; Injections, Intraperitoneal; Male; Mice; Ovalbumin; Platelet Activating Factor

Formulations consisting of egg albumin, indomethacin (IND), and olive oil or fatty acids, were prepared by vigorous stirring using a high-speed homogenizer and subsequent freeze-drying. To confirm the anti-inflammatory properties and ulcerogenic effects of the formulations, we examined the action of the formulations on carrageenan-induced edema in rats as well as their ulcerogenic actions in the same species. Compared with IND alone, albumin-IND-olive oil (9:1:4.3), albumin-IND-linolenic acid (9:1:4.3), albumin-IND-linolic acid (9:1:4.3), albumin-IND-oleic acid (9:1:4.3), albumin-IND-stearic acid (9:1:4.3), and albumin-IND-tristearin (9:1:4.3) formulations all exhibited a more potent inhibitory effect on carrageenan-induced edema. In addition, the inhibitory effects on edema formation of an albumin-IND (9:1) complex was as strong as that of IND alone. These results suggested that the bioavailability of IND was increased by olive oil, fatty acid, and tristearin as absorbefacient agents. The increase in the bioavailability was evident from the fact that the mean plasma levels, maximum plasma levels (Cmax), and area under plasma concentration-time curve (AUC) values after oral administration of the albumin-IND-olive oil (9:1:4.3) formulation was significantly greater than that after administration of the drug alone. With respect to their ulcerogenic properties, the formulations were significantly less active than IND alone, suggesting that a reduction in the ulcerogenic activity of IND was by produced complexation with egg albumin.

Topics: Administration, Oral; Animals; Biological Availability; Carrageenan; Drug Carriers; Edema; Fatty Acids; Freeze Drying; Indomethacin; Inflammation; Male; Olive Oil; Ovalbumin; Plant Oils; Rats; Rats, Sprague-Dawley; Stomach Ulcer

Anti-inflammatory properties of zinc protoporphyrin disodium (Zn-PP-2Na) were studied. Zn-PP-2Na exhibits anti-allergic action against type III and IV reactions (passive Arthus reaction in rats and tuberculin-induced footpad reaction in mice), but does not affect type I and II reactions (homologous passive cutaneous anaphylaxis in mice and reversed cutaneous anaphylaxis in rats). Zn-PP-2Na also clearly inhibits type II collagen-induced arthritis in mice. The agent inhibits general arthritis symptoms, anti-type-II collagen antibody production and type II collagen-induced delayed type hypersensitivity (DTH) in arthritic mice. Zn-PP-2Na, however, did not affect carrageenin-induced paw edema and histamine- and serotonin-induced skin reactions in rats. Zn-PP-2Na inhibits IL-1-induced mouse lymphocyte proliferation, but does not affect PMA-induced O2- generation from guinea-pig neutrophil. These results indicate that Zn-PP-2Na inhibits type II collagen-induced arthritis in mice due to the antagonism of IL-1 activity and the inhibition of DTH against type II collagen.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthus Reaction; Ascaris; Collagen; Edema; Hypersensitivity; Interleukin-1; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Ovalbumin; Oxygen Consumption; Passive Cutaneous Anaphylaxis; Protoporphyrins; Rats; Rats, Wistar; Skin Tests

Activity of myeloperoxidase (MPO) was determined in different tissues to detect granulocyte infiltration. MPO was measured in the mouse ear after injection of interleukin-1 beta, in the rat paw after carrageenan-induced edema and in the lung of sensitized guinea pigs after ovalbumin inhalation. Pretreatment of the animals with antiinflammatory drugs abolished the increase of MPO activity in tissues induced by this different stimuli.

Topics: Animals; Carrageenan; Dexamethasone; Ear; Edema; Guinea Pigs; Hindlimb; Indomethacin; Inflammation; Interleukin-1; Lung; Male; Mice; Neutrophils; Ovalbumin; Peroxidase; Rats; Rats, Sprague-Dawley

The protective effects of two antihistamines and two anti-allergic drugs against anaphylactic paw edema were studied in immunized animals that had or had not received a booster injection of antigen. The injection of 1 or 10 micrograms/paw ovalbumin induced acute paw edema of similar intensity in both groups. The antihistamine meclizine and the mixed anti histamine/anti-5-HT antagonist cyproheptadine reduced the anaphylactic reaction by 55 and 84% respectively, in non-boosted animals and were less effective against edema induced by 1 microgram antigen in boosted animals. The effectiveness of these drugs was also reduced when boosted mice were challenged with 10 micrograms antigen, where meclizine and cyproheptadine inhibited edema by 31 and 59%, respectively. The anti-allergic compounds ketotifen and azelastine, although effective against allergic inflammation in non-boosted mice, had a reduced or no effect in boosted mice. Our results suggest that allergic edema is less sensitive to antihistamine and anti-allergic drugs in boosted mice, which may be accounted for by an increased role of other mediators.

Topics: Analysis of Variance; Anaphylaxis; Animals; Drug Interactions; Edema; Histamine H1 Antagonists; Immunization; Immunoglobulin E; Immunoglobulin G; Male; Meclizine; Mice; Ovalbumin

SR 27417, the first member of a newly developed series of platelet activating factor (PAF) antagonists inhibited in a dose-dependent manner PAF-induced oedema formation in rabbit skin when administered i.d. premixed with PAF (ED50 = 3.3 +/- 0.15 pmol/site i.d. (intradermally) (n = 5). The effect of SR 27417 was over 660 times more potent than that of the triazolothienodiazepine, WEB-2086 (ED50 = 5.4 +/- 0.71 nmol/site i.d.) (n = 5). SR 27417 protected rabbits from PAF-induced plasma extravasation with an ED50 value of 16 +/- 3 micrograms/kg when given i.v. 1 h before PAF challenge. It was also effective when given p.o. 3 h before PAF i.d. administration (ED50 = 0.18 +/- 0.07 mg/kg p.o.) (n = 5). This effect of SR 27417 was selective for PAF since inflammatory responses induced by other mediators (bradykinin, histamine, N-formyl-L-methionyl-L-leucyl-L-phenyl-alanine, leukotriene B4) were not affected. After i.v. or oral administration (1 and 5 mg/kg respectively) SR 27417 had an extended duration of activity (between 72 and 96 h). In presensitized rabbits, SR 27417 premixed with the allergen inhibited dose-dependently allergen-induced plasma exudation (ED50 = 12 +/- 0.08 nmol/site i.d.) (n = 5) (vs. 850 +/- 98 nmol/site (n = 5) for WEB-2086). Similarly, i.v. injection of SR 27417 (1 mg/kg i.v.) inhibited allergen-induced vascular permeability. These results confirm that PAF plays a major role in the development of cutaneous anaphylaxis and that SR 27417 may be an effective prophylactic drug.

Topics: Allergens; Animals; Antigens; Edema; Injections, Intravenous; Male; Ovalbumin; Platelet Activating Factor; Rabbits; Skin Diseases; Thiazoles

The purpose of this study was to determine the relative contributions of airway wall edema and smooth muscle contraction to the early response (ER) of allergic bronchoconstriction. Brown Norway rats, 6 to 7 wk old, were sensitized with ovalbumin (OA). Anesthetized rats were challenged with either OA or saline 2 wk later. Pulmonary resistance (RL) was measured every minute until either it increased to 150% of the baseline, defined as a significant ER, or until 15 min elapsed. Eight OA-challenged test rats with a significant ER and eight saline-challenged control rats were used for morphometric studies. The lungs were quick-frozen with liquid nitrogen, processed with freeze substitution, and sagittal sections (5 microns) were stained with hematoxylin and eosin. The airway lumen subtended by the epithelial basement membrane (LuB) and cross sectional airway wall area (AW) of all airways were measured by camera lucida and digitization. The LuB and AW of each airway was standardized for size by dividing by the ideal airway lumen (LuBideal), which was calculated from the length of basement membrane, assuming a perfect circle in the unconstricted state. The cumulative frequency distribution of the LuB/LuBideal for the airways from test rats was shifted to the left compared with the control rats (p less than 0.01), indicating airway narrowing after challenge. Airway narrowing increased as a function of airway size. Cumulative frequency distributions of AW/LuBideal showed that there was a significant increase in the wall thickness of only the small airways of test animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allergens; Animals; Asthma; Bronchi; Bronchial Hyperreactivity; Bronchial Provocation Tests; Edema; Male; Muscle, Smooth; Ovalbumin; Rats; Rats, Inbred BN

After recovery from a first intraplantar or intrathoracic stimulation with bradykinin, repeated daily provocation with this peptide resulted in a progressive loss of its ability to cause paw or pleural oedema, reaching 0-20% of the control within seven and four consecutive provocations, respectively. The phenomenon was shown to be time reversible, since the unresponsiveness ceased when stimulations were discontinued, and localized, since paw oedema evoked by the peptide was not modified after desensitization of either the contralateral paw or the pleural cavity. Furthermore desensitization to bradykinin did not influence the pleurisy elicited by either histamine (200 micrograms/cavity), 5-hydroxytryptamine (5-HT) (100 microgram/cavity) or platelet-activating factor (PAF) (1 microgram/cavity), suggesting that the desensitization was selective. In contrast, when actively sensitized animals were submitted to bradykinin-induced tachyphylaxis, pleural exudation and leukocyte influx induced by antigen were drastically reduced, strongly implying bradykinin in this process. We demonstrated that repeated daily stimulation with bradykinin cause selective, local and reversible auto-refractoriness, which may be useful as a tool in attempting to evaluate the role of this peptide in inflammation.

Topics: Amino Acid Sequence; Animals; Azepines; Bradykinin; Diterpenes; Dose-Response Relationship, Drug; Edema; Female; Fibrinolytic Agents; Ginkgolides; Lactones; Leukocyte Count; Male; Molecular Sequence Data; Ovalbumin; Plant Extracts; Pleurisy; Rats; Rats, Wistar; Tachyphylaxis; Triazoles

A new model of active anaphylactic reaction in mice was developed. The edematogenic reaction appeared 5 min after the intraplantar injection of ovalbumin, peaked at 30 min after the antigenic challenge, and decreased thereafter. Using the non-steroidal, anti-inflammatory agents indomethacin and aspirin, we found that cyclooxygenase products do not participate in the reaction. In contrast, vasoactive amines appear to be involved, because meclizine and methysergide reduced the edema. Dexamethasone, BW755C, LY 171883 and WEB 2170 effectively interfered with the edematogenic reaction, which suggests that lipid mediators such as leukotrienes and PAF play a role in the active anaphylactic response.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Acetophenones; Anaphylaxis; Animals; Aspirin; Azepines; Cimetidine; Dexamethasone; Edema; Male; Meclizine; Methysergide; Mice; Ovalbumin; Platelet Activating Factor; Platelet Membrane Glycoproteins; Prednisolone; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Tetrazoles; Triazoles

Assessment of mouse paw edema induced by the passive allergic reaction was made by the previously reported dye-leakage method. The edema was induced by the injection of antiserum against ovalbumin into the paw, followed by the intravenous injection of ovalbumin 10 min before or 72 hr later. The latter reaction may be mainly mediated by heat-labile IgE. Both of the edemas were suppressed by pretreatment with mepyramine, methysergide, PAF-antagonists, or dexamethasone, and the latter suppressed by the lipoxygenase inhibitor AA-861, suggesting that histamine, serotonin, PAF, and leukotrienes are involved in exudate formation in these edemas.

Topics: Animals; Capillary Permeability; Edema; Exudates and Transudates; Female; Histamine; Immunoglobulin E; Immunoglobulins; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Ovalbumin; Passive Cutaneous Anaphylaxis; Platelet Activating Factor; Serotonin

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antitussive Agents; Carrageenan; Conjunctivitis; Cyclohexanes; Cyclohexenes; Edema; Erythema; Inflammation; Mice; Ovalbumin; Rats; Ultraviolet Rays

Four series of N-[(arylmethoxy)phenyl] compounds were prepared as leukotriene D4 (LTD4) antagonists. In the hydroxamic acid series, methyl 3-(2-quinolinylmethoxy)benzeneacetohydroxamate (Wy-48,422, 20) was the most potent inhibitor of LTD4-induced bronchoconstriction with an oral ED50 of 7.9 mg/kg. Compound 20 also orally inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ED50 of 3.6 mg/kg. In vitro, against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and 1-cysteine, 20 produced a pKB value of 6.08. In the sulfonyl carboxamide series, N-[(4-methylphenyl)sulfonyl]-3-(2-quinolinylmethoxy)-benzamide (Wy-49,353, 30) was the most potent antagonist. Compound 30 orally inhibited both LTD4- and ovalbumin-induced bronchoconstriction with ED50s of 0.4 and 20.2 mg/kg, respectively. In vitro, against LTD4-induced contraction of isolated guinea pig trachea, 30 produced a pKB value of 7.78. In the carboxylic acid series, which served as intermediates for the above two series, 3-(2-quinolinylmethoxy)benzeneacetic acid (Wy-46,016, 5) was the most potent inhibitor of LTD4-induced bronchoconstriction (99% at 25 mg/kg, intraduodenally); however, the pKB for this compound was disappointing (5.79). In the tetrazole series, the most potent inhibitor was 2-[[3-(1H-tetrazol-5-ylmethyl)phenoxy]methyl]quinoline (Wy-49,451, 41). The respective inhibitory ED50s were 3.0 mg/kg versus LTD4 and 17.5 mg/kg versus ovalbumin. In the isolated guinea pig trachea, 41 produced a pKB value of 6.70.

Topics: Animals; Azoles; Benzamides; Biological Assay; Bronchial Spasm; Carrageenan; Chemical Phenomena; Chemistry; Cyclooxygenase Inhibitors; Edema; Guinea Pigs; Hydroxamic Acids; Lipoxygenase Inhibitors; Molecular Structure; Muscle Contraction; Neutrophils; Ovalbumin; Quinolines; Rats; SRS-A; Structure-Activity Relationship; Tetrazoles; Trachea

The effect of intracutaneous adrenaline and noradrenaline (5 X 10(-12) and 5 X 10(-11) mol) was examined on the oedema (Evans blue dye leakage) response of rats to several inflammatory agents. The catecholamines reduced the oedema response to all agents tested except prostaglandin E1 (PGE1) which was significantly potentiated by noradrenaline (5 X 10(-11) mol), and a combination of bradykinin 5 X 10(-11) mol with PGE1 5 X 10(-10) mol which was not significantly affected by any dose of catecholamine. Adrenaline was more effective than noradrenaline in reducing oedema produced by 5-hydroxytryptamine (5HT) and histamine and by agents which release these amines (compound 48/80, dextran and antigen challenge with egg albumin in sensitized rats), but noradrenaline was more potent against bradykinin-induced oedema. The inhibitory effect of catecholamines against oedema produced by histamine and 5HT was abolished by a combination of phentolamine and propranolol. It was concluded that the oedema-inhibiting effect of catecholamines is due to alpha- and beta-adrenoreceptor mediated actions.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Catecholamines; Dextrans; Edema; Epinephrine; Inflammation; Male; Norepinephrine; Ovalbumin; p-Methoxy-N-methylphenethylamine; Rats

The development of novel anti-inflammatory drugs (AID) has been claimed to be dependent on the discovery of models of inflammation that differ from those currently used for drug screening, e.g. carrageenen paw oedema and u.v. erythema. We have thus evaluated the effect of a variety of drugs in a number of novel models of inflammation in the rat produced in the hind paw. We have utilized kaolin, zymosan, anti-rat IgG (anti-IgG) and the Reversed Passive Arthus (RPA) reaction to produce these oedema models. We found that the non-steroidal AID's, e.g. aspirin, flufenamic acid, indomethacin, naproxen, and phenylbutazone, were active in all four tests. Of the nine novel AID examined, levamisole and tetramisole demonstrated considerable activity in all four tests and dapsone was especially active in the anti-IgG and RPA tests. In contrast, the anti-rheumatic d-penicillamine was inactive in all four models. Each of the ten compounds tested which has been claimed to influence complement function, was active in the RPA but not in the kaolin model. These results are discussed in the context of the aetiology of each oedema and the suspected mode of action of the various drugs.

Topics: Animals; Anti-Inflammatory Agents; Antibodies, Anti-Idiotypic; Arthus Reaction; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Immunoglobulin G; Kaolin; Male; Ovalbumin; Rats; Stomach Ulcer; Zymosan

Bee venom, administered subcutaneously, suppressed the development of carrageenan-induced paw edema and adjuvant arthritis in the rat in a dose-related manner. A single dose of bee venom administered subcutaneously the day before or on the day of injection of complete Freund's adjuvant (CFA) effectively suppressed the development of polyarthritis. This suppressive effect decreased progressively as dosing was delayed. Bee venom was found to be most effective when mixed and injected (sub-plantar) together with CFA, the disease-inducing agent. Similarly, antigens such as egg albumin, when incorporated into CFA, and injected into the hind paw, prevented the development of arthritis. These results suggest that at least two mechanisms are involved in the anti-arthritic action of bee venom: (1) alteration of the immune response, probably via antigen competition, and (2) an anti-inflammatory action via corticosteroids or through an as yet undetermined mechanism.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; Bee Venoms; Carrageenan; Cyclophosphamide; Edema; Hydrocortisone; Male; Ovalbumin; Rats

Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Carrageenan; Dextrans; Dose-Response Relationship, Drug; Edema; Granuloma; Histamine Antagonists; Hyaluronoglucosaminidase; Male; ortho-Aminobenzoates; Ovalbumin; Rats; Time Factors

Topics: Anaphylaxis; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Edema; Edema Disease of Swine; Gallbladder; Gastric Mucosa; Immunization; Injections, Intravenous; Larynx; Ovalbumin; Swine; Swine Diseases; Vitamin E Deficiency

Topics: Animals; Aspirin; Dextrans; Disease Models, Animal; Edema; Escin; Nucleic Acids; Ovalbumin; Phenylbutazone; Rabbits; Rats; Sodium

The anti-inflammatory activity of aspirin-like drugs could derive, at least in part, by inhibiting synthesis and release of prostaglandins or rabbit aorta-contracting substance from platelets. Indeed, aggregation of platelets and the consequent release of inflammatory mediators has been frequently evoked as a factor in the development of the inflammatory reaction. The participation of platelets in acute inflammation was tested in three types of trauma in rats rendered thrombocytopenic with anti-platelet serum. Oedema in response to carrageenin, anti-platelet serum or passive cutaneous anaphylaxis was no different from the controls in thrombocytopenic rats.

Topics: Acute Disease; Animals; Blood Platelets; Carrageenan; Edema; Immune Sera; Inflammation; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Thrombocytopenia

Daily intraperitoneal doses of concanavalin A (Con A) produced a dose-related inhibition of adjuvant-induced arthritis in rats. Con A was also effective on established arthritis, markedly relieving the disease after only three doses. The inhibitory effect of Con A was neutralised by pre-incubation with ovalbumin, although this treatment did not modify the delayed phlogistic action of Con A in rat paws.

Topics: Animals; Arthritis, Rheumatoid; Concanavalin A; Dose-Response Relationship, Drug; Edema; Female; Foot; Hindlimb; Immunosuppressive Agents; Ovalbumin; Rats; Time Factors

The antiphlogistic effect of aurothioglucose was examined in reversed passive Arthus reaction, delayed-type hypersensitivity and carrageenan oedema. A close association existed between the antiphlogistic effect of aurothioglucose and the pathogenetic role of polymorphonuclear leukocytes. In reversed passive Arthus reaction and in carrageenan oedema the drug decreased the inflammation considerably, whereas in delayed hypersensitivity, where the leukocytes play a less important part, it exerted only a mitigating effect.

Topics: Animals; Arthus Reaction; Aurothioglucose; Carrageenan; Edema; Female; Gold; Guinea Pigs; Hypersensitivity, Delayed; Injections, Intradermal; Neutrophils; Ovalbumin; Rats

From the screening of a number of new pyrazole derivatives, the title compound, PZ-177, was selected as the most significant derivative for analgestic and anti-edematous actions, in this paper, we report the anti-edematous activity of PZ-177 as assessed by detailed analysis. PZ-177 showed a markedly inhibitory effect against rat paw edema induced by various phlogists (carragenin, dextran, egg albumin, serotonin, formalin and bradykinin). It also inhibited edema induced by anti-rat rabbit serum. The activity of PZ-177 was more potent than that of mepirizole and the same as that of phenylbutazone. Though this agent has a central depressive effect, it is considered that the action has actually little influence on anti-edematous effect, as carrageenin-induced edema was inhibited in spinal rats. On the other hand, the anti-edematous effect of PZ-177 was reduced significantly in adrenalectomized rats. It is therefore suggested that the potent anti-edematous action of PZ-177 is exerted partially by a direct action at the inflamed site and mediated partially by stimulation of the hypophysis-adrenal system.

Topics: Animals; Anti-Inflammatory Agents; Bradykinin; Carrageenan; Drug Evaluation, Preclinical; Edema; Epirizole; Formaldehyde; Ovalbumin; Pyrazoles; Rats; Serotonin

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Deficiency Diseases; Depression, Chemical; Diet; Edema; Fatty Acids, Essential; Hindlimb; Indomethacin; Kaolin; Male; Ovalbumin; Rats

Topics: Animals; Arthritis; Aspirin; Carrageenan; Croton Oil; Edema; Foot; Granuloma; Hindlimb; Hydrocortisone; Inflammation; Male; Methods; Mycobacterium; Ovalbumin; Phenylbutazone; Prostaglandins; Rats; Serotonin

Topics: Amines; Analgesics; Animals; Anti-Inflammatory Agents; Benzyl Compounds; Body Temperature; Carrageenan; Edema; Formaldehyde; Guinea Pigs; Lethal Dose 50; Male; Methylamines; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Piperazines; Pyrazoles; Rats; Stomach Ulcer; Structure-Activity Relationship; Thiazoles

Topics: Adrenocorticotropic Hormone; Aminopyrine; Animals; Anti-Inflammatory Agents; Aspirin; Carrageenan; Dextrans; Dimethyl Sulfoxide; Disease Models, Animal; Edema; Flufenamic Acid; Formaldehyde; Granuloma; Indomethacin; Inflammation; Kaolin; Male; Mefenamic Acid; Ovalbumin; Oxyphenbutazone; Phenylbutazone; Prednisolone; Rats; Sodium Salicylate; Trypsin

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Arthritis; Calcium; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Edema; Erythema; Granuloma; Hemolysis; Hyaluronoglucosaminidase; Indicators and Reagents; Male; Malonates; Mice; Ovalbumin; Phenylbutazone; Phenylhydrazines; Prednisolone; Protein Denaturation; Radiation Injuries, Experimental; Rats; Serotonin; Ultraviolet Rays; Wound Healing

Topics: Animals; Arthritis; Arthus Reaction; Bradykinin; Capillary Permeability; Carrageenan; Depression, Chemical; Dextrans; Disease Models, Animal; Dogs; Edema; Exudates and Transudates; Female; Formaldehyde; Granuloma; Guinea Pigs; Histamine; Hyaluronoglucosaminidase; Kaolin; Lymph; Male; Mice; Mycobacterium Infections; Ovalbumin; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plants, Medicinal; Rabbits; Rats; Serotonin; Species Specificity; Swine

1. Carrageenin oedema is suppressed by pre-treating the rats with cellulose sulphate, a kininogen depleting agent. This inhibition is closely related to the dose of cellulose sulphate and to the time course of kininogen depletion.2. Oedema induced by egg white or by dextran, in which the mediators are histamine and 5-hydroxytryptamine, is quite unaffected by cellulose sulphate treatment.3. Carrageenin injected intravenously lowers the arterial blood pressure of rats. This hypotensive effect is unaffected by histamine antagonists and is abolished by protease inhibitors and thus seems to be due to kinin release from plasma substrates.4. Like cellulose sulphate, carrageenin enhances the esterolytic activity of the blood from treated rats when incubated with benzoyl-arginine ethyl ester.5. The ability of carrageenin to activate the kinin-forming system could account for both its inflammatory and hypotensive effects.

Topics: Animals; Antifibrinolytic Agents; Blood Pressure; Carrageenan; Cellulose; Depression, Chemical; Dextrans; Edema; Histamine H1 Antagonists; Hypotension; Kinins; Male; Ovalbumin; Peptides; Rats; Trypsin Inhibitors

Topics: Acetylcholine; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Atropine; Croton Oil; Depression, Chemical; Edema; Exudates and Transudates; Female; Formaldehyde; Glycosides; Granuloma; Guinea Pigs; Histamine H1 Antagonists; In Vitro Techniques; Intestines; Male; Ovalbumin; Papaverine; Parasympatholytics; Phenylbutazone; Plant Extracts; Plants, Medicinal; Rabbits; Rats

Topics: Anaphylaxis; Animals; Capillary Permeability; Chlorides; Corticosterone; Depression, Chemical; Diuresis; Dogs; Edema; Female; Glycosides; Guinea Pigs; Injections, Intravenous; Male; Mice; Ovalbumin; Plants, Medicinal; Potassium; Rabbits; Rats; Sodium; Solubility; Species Specificity; Stimulation, Chemical; Terpenes

Topics: Animals; Antigens; Arthus Reaction; Dextrans; Edema; Fibrinolysis; Formaldehyde; Immune Sera; Ovalbumin; Rats; Skin

Topics: Animals; Aprotinin; Dextrans; Edema; Foot Diseases; Formaldehyde; Kallikreins; Ovalbumin; Povidone; Rats; Serotonin; Silicon Dioxide; Time Factors; Yeast, Dried

Topics: Abomasum; Anaphylaxis; Animals; Antibody Formation; Cattle; Cattle Diseases; Digestive System; Edema; Hyperemia; Intestine, Small; Lung; Ovalbumin; Pulmonary Edema; Pulmonary Emphysema

Topics: Acetates; Anaphylaxis; Animals; Calcinosis; Depression, Chemical; Edema; Exudates and Transudates; Female; Hindlimb; Hypercalcemia; Lead; Ovalbumin; Phosphorus; Rats; Sodium Salicylate; Time Factors

Topics: Animals; Antigen-Antibody Complex; Arthus Reaction; Capillaries; Chickens; Edema; Fluorescent Antibody Technique; Foot; Hindlimb; Histological Techniques; Immune Sera; Injections, Intradermal; Injections, Intravenous; Leukocytes; Male; Microscopy, Fluorescence; Ovalbumin; Rabbits; Rats; Skin; Time Factors; Veins

Topics: Adrenal Glands; Animals; Catecholamines; Dextrans; Edema; Epinephrine; Indomethacin; Myocardium; Norepinephrine; Ovalbumin; Rats

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Croton Oil; Edema; Exudates and Transudates; Female; Foreign Bodies; Formaldehyde; Glycosides; Gossypium; Granuloma; Hydrocortisone; Ovalbumin; Phenylbutazone; Rats

Topics: Animals; Anti-Inflammatory Agents; Antivenins; Bees; Capillary Permeability; Capillary Resistance; Carrageenan; Dextrans; Edema; Exudates and Transudates; Female; Formaldehyde; Guinea Pigs; Kaolin; Male; Ovalbumin; p-Methoxy-N-methylphenethylamine; Polyurethanes; Povidone; Rats; Saponins; Seeds; Serotonin Antagonists; Tea

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Dextrans; Dimethyl Sulfoxide; Drug Synergism; Edema; Formaldehyde; Heparin; Histamine H1 Antagonists; Male; Ovalbumin; Phenylbutazone; Rats; Serotonin

Topics: Adrenocortical Hyperfunction; Animals; Dextrans; Edema; Formaldehyde; Hindlimb; Lathyrism; Male; Nitriles; Ovalbumin; Rats; Serotonin

Topics: Animals; Dexamethasone; Drug Synergism; Edema; Ovalbumin; Plants, Medicinal; Rats

Topics: Anaphylaxis; Edema; Electrons; Guinea Pigs; Hypersensitivity, Delayed; Macrophages; Microscopy; Microscopy, Electron; Ovalbumin; Research; Skin; Toxicology

Topics: Animals; Carrageenan; Dextrans; DNA; Edema; Formaldehyde; Ovalbumin; Rats; Thymus Gland; Tissue Extracts

Topics: Dextrans; Edema; Hypersensitivity; Immune System Diseases; Ovalbumin; Ovomucin; Proteins; Serotonin

Topics: Animals; Chloroquine; Dextrans; Edema; Hypersensitivity; Immune System Diseases; Ovalbumin; Rats

Topics: Animals; Diabetes Mellitus, Experimental; Edema; Egg White; Ovalbumin; Rats

Topics: Adrenal Glands; Animals; Anti-Allergic Agents; Dextrans; Edema; Histamine H1 Antagonists; Ovalbumin; Promethazine; Rats

Topics: Albumins; Animals; Edema; Ovalbumin; Rats; Syndrome