prostaglandin-d2 and Edema

Topics: Animals; Arachidonic Acids; Arthritis, Rheumatoid; Edema; Eosinophils; Guinea Pigs; Humans; Hypersensitivity; Leukotriene B4; Mast Cells; Mice; Muscle Contraction; Nephritis; Prostaglandin D2; Prostaglandins; Prostaglandins D; Rabbits; Rats; Receptors, Fc; Receptors, IgE; Receptors, Immunologic; SRS-A; Thromboxanes

A sensitive, specific, and accurate high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the quantification of prostaglandins D2 (PGD2) and E2 (PGE2) in a mouse ear edema model. We used activated charcoal to obtain PG-free ear samples. The chromatographic separation was performed using a Hypersil Gold C18 column. The limit of detection of each PG was 0.4 ng mL-1, and the intra- and inter-assay estimates of precision and accuracy were <14.5 and 94.2-102.9%, respectively. Stability studies showed that all analytes were stable under various storage conditions and analytical processes. The developed and validated method was successfully used to investigate the anti-inflammatory effects of cultured bear bile powder (CBBP) by quantitatively determining PGE2 and PGD2 levels in mouse ear edema samples. These results showed that CBBP significantly inhibited the xylene-induced ear edema in mice and reversed the xylene-induced elevation of PGE2 and PGD2 levels. These results provide useful data about the anti-inflammatory bioactivities in tissues, mediated by the reduction of PGE2 and PGD2 levels, and may further encourage research and development studies of CBBP for its use as an anti-inflammatory agent.

Topics: Animals; Chromatography, High Pressure Liquid; Chromatography, Liquid; Edema; Mice; Prostaglandin D2; Tandem Mass Spectrometry

To overcome negative adverse effects and improve therapeutic index of dexamethasone (Dex) in rheumatoid arthritis (RA), we developed a novel sustained release formulation-intra-articular injectable dexamethasone-loaded thermosensitive hydrogel (DLTH) with chitosan-glycerin-borax as carrier for the remission of inflammation and pain. The focus of this article is to explore both anti-inflammatory and pain-relieving effects of DLTH joint injection in bovine type-II collagen-induced arthritis (CIA) rats.. Wistar rats were randomized into three groups, including the normal group (n=6), the model group (n=6) and the DLTH group (n=10). Joint injection of DLTH (1mg/kg Dex per rat) was injected on day 12 in the DLTH group twice a week for three weeks. Clinical signs of body weight, paw swelling and arthritis scores, histologic analysis, hind paw mechanical withdrawal threshold (MWT), plantar pressure pain threshold (PPT) were taken into consideration. Serum contents of IL-17A, prostaglandin E2 (PGE2), prostacyclin 2 (PGI2) and prostaglandin D2 (PGD2), real-time polymerase chain reaction (PCR) analysis of inflammatory factors and pain-related mediators in synovium and dorsal root ganglia (DRG), Western blotting of NF-κB in synovium were all evaluated.. Paw swelling, arthritis scores and joint inflammation destruction were all attenuated in the DLTH-treated group. Results showed that DLTH not only down-regulated serum IL-17A, but also mRNA levels of inflammatory factors and NGF, and key proteins contents of the NF-κB pathway in synovium. Increases of MWT and PPT in DLTH-treated rats elucidated pain-reducing effects of DLTH. Elevated serum PGD2 levels and declines of serum PGE2 and PGI2, and inflammatory and pain-related genes in DRGs in the DLTH group were also recorded.. These data elucidated that DLTH joint injection impeded synovial inflammation processes through down-regulating transcription activity of NF-κB pathway, and intra-articular DLTH may aid in the regulation of RA pain through regulating inflammation and pain conduction process.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Body Weight; Dexamethasone; Dinoprostone; Edema; Ganglia, Spinal; Hydrogels; Inflammation; Interleukin-17; Male; NF-kappa B; Pain; Pain Threshold; Prostaglandin D2; Rats; Rats, Wistar; Synovial Membrane

This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.

Topics: Animals; Cell Line, Tumor; Cell Survival; Cyclooxygenase 1; Cyclooxygenase 2 Inhibitors; Dinoprostone; Edema; Elasmobranchii; Etoricoxib; Fish Venoms; Histamine; Histamine H1 Antagonists; Leukocytes; Male; Mast Cells; Membrane Proteins; Mice; Promethazine; Prostaglandin D2; Pyridines; Rats; Sulfones

Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NFκB-driven pro-inflammatory signals can amplify a relatively small amount of vascular damage, resulting in progressive endothelial dysfunction to create a severe ischemic lesion. This process can be minimized by 15-deoxy-Δ(12,14)-prostaglandin J2 (PGJ(2)), an analog of the metabolically active PGD(2) metabolite. We evaluated PGJ(2)'s effects and mechanisms using rodent anterior ischemic optic neuropathy (rAION); an in vivo white matter ischemia model. PGJ(2) administration systemically administered either acutely or 5 hours post-insult results in significant neuroprotection, with stereologic evaluation showing improved neuronal survival 30 days post-infarct. Quantitative capillary vascular analysis reveals that PGJ(2) improves perfusion at 1 day post-infarct by reducing tissue edema. Our results suggest that PGJ(2) acts by reducing NFκB signaling through preventing p65 nuclear localization and inhibiting inflammatory gene expression. Importantly, PGJ(2) showed no in vivo toxicity structurally as measured by optic nerve (ON) myelin thickness, functionally by ON-compound action potentials, on a cellular basis by oligodendrocyte precursor survival or changes in ON-myelin gene expression. PGJ(2) may be a clinically useful neuroprotective agent for ON and other CNS infarcts involving white matter, with mechanisms of action enabling effective treatment beyond the currently considered maximal time for intervention.

Topics: Animals; Brain; Capillaries; Cerebral Infarction; Edema; Male; Neuroprotective Agents; NF-kappa B; Optic Nerve; Optic Neuropathy, Ischemic; Prostaglandin D2; Rats; Rats, Sprague-Dawley; Signal Transduction; Stroke; Time Factors

Systemic administration of thiazolidinediones reduces peripheral inflammation in vivo, presumably by acting at peroxisome proliferator-activated receptor gamma (PPARgamma) in peripheral tissues. Based on a rapidly growing body of literature indicating the CNS as a functional target of PPARgamma actions, we postulated that brain PPARgamma modulates peripheral edema and the processing of inflammatory pain signals in the dorsal horn of the spinal cord. To test this in the plantar carrageenan model of inflammatory pain, we measured paw edema, heat hyperalgesia, and dorsal horn expression of the immediate-early gene c-fos after intracerebroventricular (ICV) administration of PPARgamma ligands or vehicle. We found that ICV rosiglitazone (0.5-50 microg) or 15d-PGJ(2) (50-200 microg), but not vehicle, dose-dependently reduced paw thickness, paw volume and behavioral withdrawal responses to noxious heat. These anti-inflammatory and anti-hyperalgesia effects result from direct actions in the brain and not diffusion to other sites, because intraperitoneal and intrathecal administration of rosiglitazone (50 microg) and 15d-PGJ(2) (200 microg) had no effect. PPARgamma agonists changed neither overt behavior nor motor coordination, indicating that non-specific behavioral effects do not contribute to PPAR ligand-induced anti-hyperalgesia. ICV administration of structurally dissimilar PPARgamma antagonists (either GW9662 or BADGE) reversed the anti-inflammatory and anti-hyperalgesic actions of both rosiglitazone and 15d-PGJ(2). To evaluate the effects of PPARgamma agonists on a classic marker of noxious stimulus-evoked gene expression, we quantified Fos protein expression in the dorsal horn. The number of carrageenan-induced Fos-like immunoreactive profiles was less in rosiglitazone-treated rats as compared to vehicle controls. We conclude that pharmacological activation of PPARgamma in the brain rapidly inhibits local edema and the spinal transmission of noxious inflammatory signals.

Topics: Anilides; Animals; Benzhydryl Compounds; Brain; Central Nervous System Agents; Disease Models, Animal; Edema; Epoxy Compounds; Gene Expression; Inflammation; Male; Pain; PPAR gamma; Prostaglandin D2; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Rosiglitazone; Spinal Cord; Thiazolidinediones

NC/Nga (NC) mice, spontaneously develop an eczematous atopic dermatitis (AD)-like skin lesion when kept under conventional condition (Conv), but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model of AD. We have previously shown that PGD(2) and arachidonic acid inhibited the scratching behaviour of NC mice, while indomethacin enhanced it. This study was designed to assess the role of cyclooxygenase (COX)-1 and COX-2 in the itch-related scratching behaviour of NC mice. We examined the expression of COX in the skin using real-time PCR and Western blotting and the effects of SC-560 (a COX-1 selective inhibitor) or NS-398 (a COX-2 selective inhibitor) on scratching behaviour in relation to skin prostaglandin (PG) levels in NC mice. COX-1 mRNA expression was unchanged and protein expression decreased in Conv NC mice compared with that of SPF mice. By contrast, COX-2 mRNA and protein expression increased in Conv NC mice. SC-560 increased scratching behaviour and significantly reduced skin PGD(2), PGE(2) and PGF(2alpha) levels, but NS-398 did not have effects on scratching and skin PG level. Moreover, the topical application of PGD(2), which might be the endogenous inhibitor of itching, suppressed the SC-560-induced enhancement of scratching behaviour by NC mice. These results suggest COX-1-coupled skin PGD(2) biosynthesis plays a physiological role in inhibiting regulation of pruritus in NC mice with AD.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Carrageenan; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dermatitis, Atopic; Edema; Mice; Nitrobenzenes; Prostaglandin D2; Pruritus; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1% inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7-day model of multiple treatment of TPA (38.1% inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin E2 production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

Topics: Acetic Acid; Angelica; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Asteraceae; Bone Marrow Cells; Cells, Cultured; Dose-Response Relationship, Drug; Drug Combinations; Edema; Glucosamine; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Pain; Plant Extracts; Prostaglandin D2; Tetradecanoylphorbol Acetate

The transcription factor heat shock factor 1 (HSF1) plays a key role in the expression of several genes, such as heat shock protein (hsp) genes, which are cytoprotective against several pathological conditions, including inflammation. Cyclopentenone prostaglandins (cyPG) are able to activate HSF1 and induce the synthesis of the 70-kDa hsp (hsp70) in mammalian cells. These molecules are characterized by the presence of a reactive alpha,beta-unsatured carbonyl group in the cyclopentane ring (cyclopentenone) which is the key structure for triggering HSF1 activation. In the present study, we investigated, in carrageenin hind-paw edema, an acute model of inflammation, the effect of double-stranded oligodeoxynucleotides with consensus HSF1 sequence as transcription factor decoys to inhibit HSF1 binding to native DNA sites. We show that HSF1 activation and hsp72 expression occurs in inflamed tissue and that this effect is associated with the remission of the inflammatory reaction. Moreover, we studied the effect of prostaglandin 15-deoxy-delta12,14-prostaglandin (PG) J2, of its precursor, PGD2 and, for the first time in vivo, the effect of the cyclopentenone ring structure itself, 2-cyclopenten-1-one. Our results demonstrated that all agents used had anti-inflammatory properties and that this effect was associated with HSF1-induced hsp72 expression in vivo, suggesting that the use of cyclopentenone derivatives may represent a novel therapeutic approach to the treatment of inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Cyclopentanes; DNA-Binding Proteins; Edema; Heat Shock Transcription Factors; Heat-Shock Proteins; Heat-Shock Response; HSP72 Heat-Shock Proteins; Male; Prostaglandin D2; Rats; Rats, Wistar; Time Factors; Transcription Factors

Arachidonic acid (AA) mainly released from the cell membrane by phospholipase A(2) (PLA(2)) is converted to eicosanoids by the action of cyclooxygenase (COX) and lipoxygenase (LO). In order to find the specific inhibitors of AA metabolism especially PLA(2) and COX-2, 300 plant extracts were evaluated for their inhibitory activity on PGD(2) production from cytokine-induced mouse bone marrow-derived mast cells in vitro. From this screening procedure, the methanol extract of Salvia miltiorrhiza was found to inhibit PGD(2) production and the ethyl acetate subfraction gave the strongest inhibition of five subfractions tested. From this ethyl acetate subfraction, an activity-guided isolation finally gave tanshinone I as an active principle. This investigation deals with the effects of tanshinone I on AA metabolism from lipopolysaccharide (LPS)-induced RAW 264.7 cells and in vivo antiinflammatory activity. Tanshinone I inhibited PGE(2) formation from LPS-induced RAW macrophages (IC(50) = 38 microM). However, this compound did not affect COX-2 activity or COX-2 expression. Tanshinone I was found to be an inhibitor of type IIA human recombinant sPLA(2)(IC(50) = 11 microM) and rabbit recombinant cPLA(2) (IC(50) = 82 microM). In addition, tanshinone I showed in vivo antiinflammatory activity in rat carrageenan-induced paw oedema and adjuvant-induced arthritis.

Topics: Abietanes; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arthritis, Experimental; Blotting, Western; Carrageenan; Cyclooxygenase 2; Dose-Response Relationship, Drug; Edema; Humans; Inhibitory Concentration 50; Isoenzymes; Male; Mast Cells; Membrane Proteins; Mice; Phenanthrenes; Phytotherapy; Plant Extracts; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Rabbits; Rats; Rats, Sprague-Dawley; Salvia miltiorrhiza

Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Therefore, XPA-deficient mice are a useful model of human XP and represent a promising tool for photobiologic studies of the disorder. Exposure to ultraviolet (UV) B (280-320 nm) radiation greatly enhanced inflammation and immunosuppression in these mice. To investigate the molecular mechanisms of enhanced UV inflammation and immunosuppression, we determined the amount of prostaglandin (PG) E2, an inflammatory mediator and immunomodulator, and analysed the expression of cyclooxygenase (COX) mRNA in the ear skin of XPA-deficient mice after UV irradiation. In XPA-deficient mice, the amount of PGE2 significantly increased at 48 and 72 h after UVB irradiation to the level that was 8- and 16-fold higher than those in wild-type mice, respectively. The expression level of COX-2 mRNA increased in a time-dependent manner, although COX-1 mRNA was constantly expressed. Treatment with indomethacin, a potent inhibitor of PG biosynthesis, inhibited UV-induced ear swelling, abrogated local immunosuppression, and decreased the amount of PGE2 in the ear skin of XPA-deficient mice. These results indicate that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation may induce COX-2 expression. The induced production of PGE2 may be involved in the enhanced inflammation and immunosuppression caused by UV radiation in XPA-deficient mice and XP patients.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cytosol; Dinoprost; Dinoprostone; Disease Models, Animal; Ear; Edema; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Immune Tolerance; Indomethacin; Isoenzymes; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Phospholipases A; Photosensitivity Disorders; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Ultraviolet Rays; Xeroderma Pigmentosum

This study examined the pro- and anti-inflammatory effects of the stable prostaglandin (PG) D2 analogue, ZK 118.182 and the mechanism by which prostaglandins may exert their anti-inflammatory activity. Co-injected locally, ZK 118.182, like PGE2 and PGD2, dose-dependently increased plasma leakage induced by intradermal injection of bradykinin in rabbit skin. Infused i.v., ZK 118.182 (0.45 microgram/kg/min), a dose which did not affect systemic blood pressure, inhibited oedema formation in rabbit skin induced by the neutrophil-dependent agonists, formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). However, it did not modify plasma leakage induced by the neutrophil-independent mediators, bradykinin and platelet-activating factor (PAF). In contrast, neutrophil accumulation in response to LTB4 and FMLP was not affected in animals infused with ZK 118.182. In vitro, ZK 118.182, like PGE2 and PGD2 inhibited FMLP-induced superoxide anion (O2-) production by rabbit neutrophils. The compound, however, had minimal effects on O2- production induced by phorbol myristate acetate (PMA). ZK 118.182 inhibited to a small extent FMLP but not PMA-induced neutrophil adherence. These results show that depending on the route of administration, the PGD2 analogue, ZK 118.182, exhibits either pro- or anti-inflammatory effects. The anti-inflammatory effect may be related to the ability of the compound to inhibit increased microvascular permeability induced by neutrophil activation without interfering with neutrophil accumulation. This latter effect may be due to the analogue's capacity to suppress neutrophil secretion to a greater extent than neutrophil adherence.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Dinoprost; Edema; In Vitro Techniques; Indium Radioisotopes; Inflammation Mediators; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Aggregation Inhibitors; Prostaglandin D2; Rabbits; Skin; Superoxides

Magnolol, isolated from Magnolia officinalis, inhibited mouse hind-paw edema induced by carrageenan, compound 48/80, polymyxin B and reversed passive Arthus reaction. Acetic acid-induced writhing response was depressed by magnolol, indomethacin and ibuprofen. The lethality of endotoxin challenge was reduced by pretreatment with magnolol, indomethacin and BW755C, a dual cyclo-oxygenase/lipoxygenase inhibitor. The recovered myeloperoxidase activity in edematous paw was significantly decreased in mice pretreated with magnolol and BW755C. Suppression of edema was demonstrated not only in normal mice but also in adrenalectomized animals. Magnolol was less potent on reducing PGD2 formation in rat mast cell than that of indomethacin. Unlike dexamethasone, magnolol did not increase liver glycogen level. The results suggest that the anti-inflammatory effect of magnolol was neither mediated by glucocorticoid activity nor through releasing steroid hormones from adrenal gland. The action of magnolol is proposed to be dependent on reducing the level of eicosanoid mediators.

Topics: Adrenalectomy; Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Dexamethasone; Edema; Female; Indomethacin; Lignans; Liver; Mice; Mice, Inbred ICR; Peroxidase; Polymyxin B; Prostaglandin D2; Rats; Rats, Wistar

Prostaglandin D2 (PGD2) and thromboxane A2 (TXA2) have been suggested to play important roles in the pathogenesis of bronchial asthma. In the present study, effects of i.v.-administration of PGD2 on bronchial hyperresponsiveness in guinea pigs were investigated by the measurement of dynamic compliance and dynamic respiratory resistance with formulae which can exclude the effects of changes of the airway wall thickness. With these formulae, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of PGD2 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was enhanced with the administration of PGD2. Moreover, TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the effect of PGD2 administration.

Topics: Airway Resistance; Animals; Asthma; Bridged Bicyclo Compounds; Bronchial Hyperreactivity; Edema; Fatty Acids, Monounsaturated; Guinea Pigs; Histamine; Infusions, Intravenous; Male; Muscle Contraction; Muscle, Smooth; Prostaglandin D2; Thromboxane A2

The relative potencies of PGD2, PGE2 and PGI2 in potentiating bradykinin-induced hyperalgesia and oedema were determined in the paws of aspirin-treated guinea-pigs. PGE2 and to a lesser degree PGD2 but not PGI2, potentiated bradykinin-induced hyperalgesia, whereas PGD2, but not PGE2 or PGI2, potentiated oedema. These findings differ from those in other species, and possibly reflect interspecies differences in modulation of inflammatory reactions by prostanoids.

Topics: Animals; Aspirin; Bradykinin; Dinoprostone; Edema; Epoprostenol; Female; Guinea Pigs; Pain; Prostaglandin D2; Prostaglandins; Sensory Thresholds

The putative modulatory role of central prostaglandins (PGs) on peripheral inflammation has been explored by investigating the effects of intracerebroventricularly (i.c.v.) administered PGD2, the major rodent brain PG, hydrocortisone, a phospholipase A2 inhibitor, and the cyclo-oxygenase inhibitors, paracetamol and mefenamic acid, on carrageenan-induced paw inflammation in rats. PGD2 produced a dose-related inflammation-augmenting effect, whereas hydrocortisone and the PG synthesis inhibitors, paracetamol and mefenamic acid, induced attenuation of the peripheral oedema. These findings confirm an earlier report from this laboratory which had indicated that central PGs may modulate peripheral inflammation and that conventional anti-inflammatory agents exert at least part of their effect by inhibiting central PG synthesis.

Topics: Acetaminophen; Animals; Carrageenan; Dose-Response Relationship, Drug; Edema; Female; Hydrocortisone; Injections, Intraventricular; Male; Mefenamic Acid; Prostaglandin Antagonists; Prostaglandin D2; Rats; Rats, Inbred Strains

The skin response to UVB irradiation in mice was evaluated by means of ear swelling. ICR albino mice were irradiated with 500 mJ/cm2 UVB and the effect of various drugs on ear swelling was examined 24 h after irradiation. Intravenous injections of betamethasone (0.8 microgram/g body wt.) or indomethacin (24 micrograms/g) remarkably inhibited ear swelling, whereas intraperitoneal injections of diphenhydramine (20 micrograms/g), cimetidine (10 micrograms/g), or a combination of both these antihistamines did not. In contrast, the number of sunburn cells counted 24 h after UVB irradiation (200 mJ/cm2) in mouse ears was not affected by these drugs. The amount of prostaglandin D2 (PGD2) in mice ears at various intervals after irradiation with 500 mJ/cm2 UVB was determined by radioimmunoassay. Compared with the values before irradiation, the PGD2 levels were significantly higher 3 and 6 h after irradiation and gradually decreased and returned to the basal level by 12 h, although ear swelling continued after 12 h. These results suggest that prostaglandins are responsible at least in part for the development of ear swelling, but not for sunburn cell formation induced by UVB, and that ear swelling represents a simple and useful response model for the rapid in vivo screening of nonsteroidal or steroidal anti-inflammatory agents.

Topics: Animals; Betamethasone; Cimetidine; Diphenhydramine; Ear, External; Edema; Erythema; Indomethacin; Male; Mice; Mice, Inbred ICR; Prostaglandin D2; Prostaglandins D; Skin; Ultraviolet Rays