leukotriene-b4 and Dermatitis--Atopic

Atopic dermatitis is clearly characterized by altered cutaneous physiologic responses. There is a tendency to acral vasoconstriction. Rubbing causes skin pallor and white dermographism. Vascular instability is demonstrated by responses to cholinergic agents, histamine, and nicotinates. Psychophysiologic studies demonstrate exaggerated vasodilator responses to emotional stress with consequent pruritus and scratching. The itch threshold is low, duration is prolonged, and nighttime scratching movements may be frequent or almost continuous. Regardless of the inciting trigger factors, the scratching causes the damage and the severe dermatitis. Thermal as well as emotional stimuli to sweating cause severe itching in AD, yet the concept of a miliaria-type, poral occlusion mechanism remains unproven. Some studies suggest actually increased sweating along with erythema and pruritus during acute flares of AD. The concept of sweat-borne allergens causing skin reactions during sweating is interesting but has never been proven. Studies of sweat responses to pharmacologic agents have produced conflicting data, and attempts to link these responses to Szentivanyi's beta-adrenergic blockade theory are not convincing. The numerous variables of climate, season, sex, age, and habitus affect sweating greatly. Future studies must carefully control for each of these factors before pharmacologically induced sweat responses can be interpreted clearly. A number of lines of evidence suggest involvement of histamine and other mediators in the evolution of erythema, pruritus, and scratching in AD. Flares of the condition have been reproducibly evoked by only two incitants: experimental emotional stress interviews and specific food challenge in selected sensitive individuals. In the latter, increased plasma histamine has been demonstrated, presumably generated by antigen/IgE stimulated degranulation of mast cells in the gut and/or skin. The demonstrated increased histamine releasability of basophils from atopic individuals may be the result of defective cellular regulatory mechanisms. Recent studies have demonstrated increased cyclic AMP-phosphodiesterase activity in leukocytes from atopic individuals. The resultant decreased intracellular cyclic AMP removes an inhibitory factor, which in turn causes net cellular hyperresponsiveness. This effect has been shown to account, at least in part, for increased histamine release from leukocytes of patients with AD. These and other studies foc

Topics: Biofeedback, Psychology; Catecholamines; Cyclic AMP; Dermatitis, Atopic; Female; Histamine; Humans; Leukotriene B4; Lipid Metabolism; Menstruation; Nicotinic Acids; Parasympathomimetics; Pregnancy; Pruritus; Receptors, Histamine H2; Skin; Skin Temperature; Sweat Glands; Sympathomimetics; T-Lymphocytes; T-Lymphocytes, Regulatory; Thyroid Gland; Virulence Factors, Bordetella

We have studied the effect of a nonsedating antihistamine, cetirizine dihydrochloride, on the in vitro chemotaxis of leukocytes from human peripheral blood. We observed that 0.25 microgram/ml of cetirizine dihydrochloride in vitro significantly inhibited the chemotaxis of monocytes toward N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4. Higher concentrations of cetirizine, 1.0 and 2.5 micrograms/ml, completely inhibited monocyte chemotaxis without affecting cell viability. T-lymphocyte migration was also significantly depressed but not abolished. Pyrilamine (mepyramine) was not inhibitory in equimolar concentrations. According to these in vitro observations, we extended our studies to measure monocyte and T-lymphocyte chemotaxis in an open study, where four healthy volunteers and six patients with atopic dermatitis took 10 and 20 mg/day cetirizine 3 days. We observed a reduction in ex vivo monocyte and T-lymphocyte chemotaxis toward N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 without a reduction of the blood cell count. The results were confirmed in an ensuing double-blind, placebo-controlled study of 16 healthy subjects and 14 adult patients with atopic dermatitis, where ex vivo monocyte chemotaxis was reduced or abolished during cetirizine therapy. Serum levels of the two eosinophil-derived granule proteins, eosinophilcationic protein P and eosinophil protein X, were not changed during the treatment period of 7 days. The results show that cetirizine dihydrochloride has an inhibitory effect on monocytes and T lymphocytes in vitro and ex vivo. Our findings support the clinical observations that cetirizine dihydrochloride has an antiinflammatory effect besides its H1-blocking activity.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Cetirizine; Chemotaxis, Leukocyte; Dermatitis, Atopic; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophil Granule Proteins; Humans; Leukocytes, Mononuclear; Leukotriene B4; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Placebo Effect; Pyrilamine; Ribonucleases; T-Lymphocytes

Leukotriene B

Topics: Animals; Biomarkers; Cell Differentiation; Cell Membrane; Cell Movement; Cell Proliferation; Chemokine CCL21; Dendritic Cells; Dermatitis, Atopic; Hypersensitivity; Inflammation; Interleukin-12; Leukotriene B4; Lymph Nodes; Mice, Inbred C57BL; Receptors, Leukotriene B4; Skin; Th1 Cells; Transcriptome

Topics: Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Cyclooxygenase 2; Cytokines; Dermatitis, Atopic; Dinitrofluorobenzene; Dinoprostone; Humans; Leukotriene B4; Linoleic Acids, Conjugated; Male; Mast Cells; Mice; Myeloid Differentiation Factor 88; NF-kappa B; Signal Transduction; Skin; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis-5, 8, 11-eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B

Topics: 8,11,14-Eicosatrienoic Acid; Actins; Animals; Biomarkers; Capillary Permeability; Chemotaxis; Coconut Oil; Dermatitis, Atopic; Dermatitis, Contact; Dietary Fats, Unsaturated; Disease Models, Animal; Female; Immunohistochemistry; Immunophenotyping; Leukotriene B4; Lipid Metabolism; Mice; Neutrophils; Skin

Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although leukotriene B4 (LTB4) is involved in tissue inflammation that occurs in several disorders, including AD, therapeutic strategies based on LTB4 inhibition have not been explored. Here we demonstrate that progression of an AD-like skin disease in NC/Nga mice is inhibited when docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) is administered together with FK506. Treatment with DHA/EPA and FK506 decreases the clinical score of dermatitis in NC/Nga mice and lowers local LTB4 concentrations. The treatment also suppressed the infiltration of T cells, B cells, eosinophils and neutrophils, and promoted reduced serum IgE levels. Secretion of IL-13 and IL-17A in CD4(+) T cells was lower in DHA/EPA- and FK506-treated mice than in mice treated with FK506 alone. The inhibition of disease progression induced by DHA/EPA was reversed by local injection of LTB4, suggesting that the therapeutic effect of DHA/EPA is LTB4-dependent. Our results demonstrate that treatment of AD with DHA/EPA is effective for allergic skin inflammation and acts by suppressing LTB4 production. J. Med. Invest. 63: 187-191, August, 2016.

Topics: Animals; Dermatitis, Atopic; Docosahexaenoic Acids; Eicosapentaenoic Acid; Immunoglobulin E; Leukotriene B4; Mice; Tacrolimus

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. In the study, ultra high performance liquid chromatography-mass spectrometry was used to investigate serum metabolic abnormalities of AD children. Two batch fasting sera were collected from AD children and healthy control; one of them was for nontargeted metabolomics analysis, the other for targeted eicosanoids analysis. AD children were divided into high immunoglobulin E (IgE) group and normal IgE group. On the basis of the two analysis approaches, it was found that the differential metabolites of AD, leukotriene B4, prostaglandins, conjugated bile acids, etc., were associated with inflammatory response and bile acids metabolism. Carnitines, free fatty acids, lactic acid, etc., increased in the AD group with high IgE, which revealed energy metabolism disorder. Amino acid metabolic abnormalities and increased levels of Cytochrome P450 epoxygenase metabolites were found in the AD group with normal IgE. The results provided a new perspective to understand the mechanism and find potential biomarkers of AD and may provide a new reference for personalized treatment.

Topics: Bile Acids and Salts; Biomarkers; Carnitine; Child, Preschool; Chromatography, Liquid; Dermatitis, Atopic; Eicosanoids; Fatty Acids, Nonesterified; Female; Humans; Immunoglobulin E; Infant; Lactic Acid; Leukotriene B4; Male; Mass Spectrometry; Metabolome; Metabolomics; Prostaglandins; Reproducibility of Results; ROC Curve

Leukotrienes constitute a group of lipid mediators, which may be subdivided into two groups, with leukotriene B4 on the one hand and cysteinyl leukotrienes on the other. Although leukotrienes are abundantly expressed in skin affected by diverse chronic inflammatory diseases, including atopic dermatitis, psoriasis, pemphigus vulgaris and bullous pemphigoid, their pathological roles in these diseases have remained elusive. Recent data now reveal that both leukotriene B4 and cysteinyl leukotrienes are indispensable in the pathogenesis of atopic dermatitis, with leukotriene B4 initiating the recruitment of inflammatory cells, particularly neutrophils and TH 2 cells into the skin, and cysteinyl leukotrienes later inducing characteristic structural alterations of chronically affected skin, specifically skin fibrosis and keratinocyte proliferation. Thus, these results reveal a sequential cooperation of LTB4 and cysteinyl leukotrienes to initiate and perpetuate allergic skin inflammation. These new insights highlight leukotrienes as promising therapeutic targets in allergic skin inflammation and should encourage more research into the role of leukotrienes in other inflammatory skin diseases.

Topics: Animals; Cell Proliferation; Dermatitis, Atopic; Fibrosis; Humans; Hypersensitivity; Inflammation; Keratinocytes; Leukotriene B4; Lipids; Mice; Neutrophils; Receptors, Leukotriene; Skin; Skin Diseases; Th2 Cells

Airway inflammation may be present in subjects affected by atopic dermatitis (AD) but still without asthma symptoms. Exhaled breath condensate (EBC) reflects the composition of bronchoalveolar extracellular lining fluid that contains a large number of mediators of airway inflammation and oxidative damage..   We assessed inflammatory markers in the EBC of patients with AD. Fifty-six children (34 girls and 22 boys) were enrolled: 33 affected by AD and 23 healthy controls..   EBC was collected using a condenser device. We measured EBC pH and concentrations of leukotriene B4 (LTB4), 8-isoprostane, H(2) O(2) , malondialdehyde and 4-hydroxynoneal. Respiratory resistance was also evaluated..   EBC pH in patients with AD was significantly lower than in healthy children, median (range) being 8·02 (7·94-8·12) in AD vs. 8·11 (8·05-8·16) (P = 0·02). The values of exhaled 8-isoprostane and LTB4 were significantly increased in subjects with AD compared with normal controls (P < 0·01 and P < 0·001, respectively). There was increased 4-hydroxynoneal in patients with AD but this did not reach statistical significance. Evaluating respiratory resistance, no bronchoreversibility was demonstrated in the children with AD.. pH, LTB4 and 8-isoprostane in EBC could be sensitive markers of airway inflammation in children with AD. Prospective studies would be of interest to evaluate if airway inflammation, not yet clinically evident, could predict the development of asthma later in life in children with AD.

Topics: Airway Resistance; Aldehydes; Biomarkers; Breath Tests; Case-Control Studies; Child; Child, Preschool; Dermatitis, Atopic; Dinoprost; Female; Humans; Hydrogen-Ion Concentration; Leukotriene B4; Male; Malondialdehyde; Oxidative Stress

To elucidate the mechanisms of severe itch in atopic dermatitis, we investigated the role of leukotriene B(4) , a potent itch mediator, in spontaneous itch-related behaviour in NC mice with atopic dermatitis-like skin lesions. Topical application of the BLT leukotriene B(4) receptor antagonist ONO-4057 inhibited spontaneous itch-related behaviour. The concentration of leukotriene B(4) was significantly increased in the lesional skin. The expression levels of 5-lipoxygenase were also elevated in the lesional skin, yet present throughout the epidermis of both healthy and lesional skin. These results suggest a role for leukotriene B(4) in chronic dermatitis-related itch. Sphingosylphosphorylcholine (SPC) was increased in the epidermis of the lesional skin. Moreover, intradermal injection of SPC elicited itch-related behaviours in healthy mice. Because SPC induces itch-related responses through the production of leukotriene B(4) in keratinocytes (J Invest Dermatol, 129, 2009, 2854), these results suggest that an increase in SPC induces leukotriene B(4) -mediated itching in chronic dermatitis. BLT1 receptor and 5-lipoxygenase in the skin may be effective pharmacological targets for the treatment of itch in atopic dermatitis.

Topics: Administration, Topical; Animals; Arachidonate 5-Lipoxygenase; Dermatitis, Atopic; Disease Models, Animal; Leukotriene B4; Mice; Phenylpropionates; Phosphorylcholine; Pruritus; Receptors, Leukotriene B4; Skin; Sphingosine

Canine atopic dermatitis (AD), a chronic inflammatory skin disease, shares characteristics with its human counterpart. To get insight into the role of enzymes involved in production of prostaglandin E(2) (PGE2) and leukotriene B(4) (LTB(4)), potent inflammatory mediators originating from membrane-derived arachidonic acid (AA), expression of genes encoding these enzymes and receptors was quantified by qPCR in non-lesional and lesional skin from atopic dogs and in healthy skin. Significantly higher mRNA expression of the key enzymes 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP), leukotriene A(4) hydrolase (LTA(4)H) and prostaglandin E synthase 1 (mPGES-1) and their receptors (PGE receptors 2 and 3) were observed. Being responsible for elevated levels of metabolites of the 3-series prostaglandins and the 5-series leukotrienes these enzymes may be interesting targets for therapy that should result in amelioration of clinical signs in canine atopic dermatitis.

Topics: 5-Lipoxygenase-Activating Proteins; Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Dermatitis, Atopic; Dinoprostone; Disease Models, Animal; Dogs; Eicosanoids; Epoxide Hydrolases; Interleukin-6; Intramolecular Oxidoreductases; Leukotriene B4; Prostaglandin-E Synthases; Skin

To discover new 5-lipoxygenase (5-LO) inhibitors applicable to inflammation-related skin disease, we identified and examined antiinflammatory properties of a novel 5-LO inhibitor, KR-33749, in vitro and in vivo.. 5-LO enzyme activity was assayed using insect cell lysates overexpressing rat 5-LO. The leukotriene B(4) (LTB(4)) level was assayed in rat basophilic leukemia (RBL-1) cell line. Mouse ear edema was induced by topical application of arachidonic acid. Atopic dermatitis-like skin lesion was induced by topical application of 1-chloro-2,4-dinitrobenzene (DNCB) to NC/Nga mice.. KR-33749 inhibited 5-LO activity with an IC(50) value of 70.5 +/- 6.0 nmol/l in parallel with LTB(4) inhibition in RBL-1 cells. The compound exhibited a >1,000-fold selectivity against 12-LO and 15-LO. KR-33749 showed in vivo protective effects against arachidonic acid-induced ear edema and DNCB-induced atopic dermatitis-like symptoms in NC/Nga mice.. Our results show that KR-33749, a new 5-LO inhibitor exhibits potent antiinflammatory activities in vitro as well as in vivo.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cell Line, Tumor; Dermatitis, Atopic; Dinitrochlorobenzene; Dose-Response Relationship, Drug; Edema; Isoenzymes; Leukotriene B4; Lipoxygenase Inhibitors; Male; Mice; Mice, Inbred BALB C; Osmolar Concentration; Rats; Recombinant Proteins; Skin; Skin Diseases; Thiazoles; Time Factors; Xylenes

In atopic dermatitis, the concentration in the skin of sphingosylphosphorylcholine (SPC), which is produced from sphingomyelin by sphingomyelin deacylase, is increased. In the present study, we investigated the itch-eliciting activity of SPC and related substances and the mechanisms of SPC action in mice. An intradermal injection of SPC, but not sphingomyelin and sphingosine, induced scratching, an itch-associated response, which was not suppressed by a deficiency in mast cells or the H(1) histamine receptor antagonist terfenadine. The action of SPC was inhibited by the mu-opioid receptor antagonist naltrexone. SPC action also was inhibited by the 5-lipoxygenase inhibitor zileuton and the leukotriene B(4) antagonist ONO-4057, but not by the cyclooxygenase inhibitor indomethacin. Moreover, SPC action was inhibited by the antiallergic agent azelastine, which suppresses the action and production of leukotriene B(4). Administration of SPC to the skin and to primary cultures of keratinocytes increased leukotriene B(4) production. SPC increased intracellular Ca(2+) ion concentration in primary cultures of dorsal root ganglion neurons and keratinocytes. These results suggest that SPC induces itching through a direct action on primary afferents and leukotriene B(4) production of keratinocytes. Sphingomyelin deacylase and SPC receptors may be previously unreported targets for antipruritic drugs.

Topics: Animals; Calcium; Dermatitis, Atopic; Ganglia, Spinal; Histamine; Histamine H1 Antagonists, Non-Sedating; Injections, Intradermal; Keratinocytes; Leukotriene B4; Male; Mast Cells; Mice; Mice, Inbred ICR; Naltrexone; Narcotic Antagonists; Neurons; Phosphorylcholine; Pruritus; Skin; Sphingomyelins; Sphingosine; Terfenadine

The effect of smoke-dried bonito undigested fraction remaining after microbial protease treatment (SDBR) on a spontaneously occurring mouse model of atopic dermatitis was studied in male 5-wk-old, NC/Nga mice. Smoke-dried bonito, Katsuobushi, is a traditional Japanese food. SDBR contains 2 major components: bonito oil and protease-undigested proteins. Mice were fed a casein diet containing corn oil (C diet) or a diet containing SDBR (SDBR diet) for 18 wk. In comparison with the C diet, the SDBR diet alleviated the increase in skin severity score and plasma IgE concentration in a time-dependent manner, and lowered leucotriene B(4) (LTB(4))-releasing ability upon calcium ionophore A23187 stimulation. The SDBR diet did not affect scratching time. These results demonstrate that SDBR diet alleviates atopic dermatitis-like skin lesions in NC/Nga mice.

Topics: Animals; Behavior, Animal; Body Weight; Caseins; Corn Oil; Dehydration; Dermatitis, Atopic; Disease Models, Animal; Fish Oils; Fishes; Food Preservation; Immunoglobulin E; Leukotriene B4; Male; Mice; Mice, Inbred Strains; Peptide Hydrolases; Severity of Illness Index; Time Factors

Various markers of the inflammatory response were measured in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) from 31 dogs with atopic dermatitis (AD). The variables assayed included chemiluminescence, acid hydrolase enzyme concentrations, leukotriene B(4) (LTB(4)) production and complement C3 conversion. The results were compared to those derived from a population of clinically healthy dogs. Dogs with AD exhibited a significant increase in median LTB(4) production in PMNs compared to controls (0.94 versus 0.00 ng/10(6) cells; P<0.01). Significant increases in the median concentrations of intracellular beta-galactosidase (PBMC fraction - 0.42 versus 0.25 mU/10(6) cells; P<0.05) (PMN fraction - 0.47 versus 0.12 mU/10(6) cells; P<0.01) and beta-glucuronidase (PBMC fraction - 0.52 versus 0.27 mU/10(6) cells; P<0.05) were also evident in the AD group. Although median maximum chemiluminescence values for both leucocyte sub-populations were higher in controls, the differences recorded were not significant (P>0.05). However, the median time taken to reach maximum chemiluminescence was significantly shorter in the PMN fraction of dogs with AD (7.00 versus 10.00 min; P<0.01). Atopic dogs had a significant increase in the median percentage conversion of complement C3 to C3b (66.0 versus 57.3%; P<0.01). The results of this study indicate a priming of the inflammatory response in dogs with AD. The role of LTB(4) in the pathogenesis of canine AD and the potential efficacy of leukotriene antagonists in the treatment of this disorder warrant further investigation.

Topics: Animals; Case-Control Studies; Complement C3; Dermatitis, Atopic; Dog Diseases; Dogs; Female; Hydrolases; Leukocytes; Leukotriene B4; Luminescent Measurements; Male; Monocytes; Neutrophils

To evaluate the role of Chlamydia pneumoniae respiratory tract infection on pediatric asthma, allergic rhinitis or atopic eczema initiation, children of three age groups (n=1211) were prospectively studied for a C. pneumoniae infection using throat swabs and polymerase chain reaction (PCR) with enzyme immunoassay (EIA) detection. Infected children (study group, SG) were examined monthly until the agent could not be detected, quantifying persistent infection. They were compared with randomly selected, non-infected children without asthma matched for age, gender and origin (control group, CG) regarding lung function and inflammatory parameters as well as initiation of allergic diseases judged by family doctor diagnosis after, in median, 22 months. At the first follow-up examination, SG children revealed a higher leukotriene B4 (median 36 pg/ml vs. 19, p=0.04) and 8-isoprostane (median 15 pg/ml vs. 12, p=0.04) in breath condensate characterizing neutrophil, agent-related inflammation and oxidative stress in the lower airways. Cysteinyl leukotrienes, important in acute allergic inflammation, were without difference. Local, anti C. pneumoniae secretory immunoglobulin A antibodies were higher in children after C. pneumoniae infection (optical density median 0.7 vs. 0.4, p=0.001) confirming PCR-EIA results. At the final examination, there was no difference in pathological lung function tests, parameters of exhaled breath condensate or eosinophilia of the nasal mucosa. Incidence of asthma (0/55 vs. 5/54, p=0.03) and allergic rhinitis [3/53 vs. 10/52, p=0.04, odds ratio and 95% confidence interval-OR 0.25 (0.06;0.98)] as well as prevalence of asthma [1/56 vs. 9/58, p=0.02, OR 0.1 (0.01;0.81)] and allergic rhinitis [6/56 vs. 16/58, p=0.03, OR 0.32 (0.11;0.88)] were lower in the SG children. There was no association in atopic eczema. Three children with persistent infection revealed a slightly higher incidence in allergic rhinitis without significance than those with single C. pneumoniae detection (1/3 vs. 2/50), however, not to the CG. In conclusion a C. pneumoniae upper respiratory tract infection may be regarded as a protective factor for childhood asthma or allergic rhinitis in a population of kindergarten and school-age children.

Topics: Adolescent; Animals; Asthma; Child; Child, Preschool; Chlamydophila Infections; Chlamydophila pneumoniae; Cohort Studies; Dermatitis, Atopic; Dinoprost; Female; Humans; Immunoenzyme Techniques; Immunoglobulin A; Leukotriene B4; Male; Pneumonia, Bacterial; Polymerase Chain Reaction; Respiratory Function Tests; Rhinitis

Chemoattractant receptor-homologous molecule expressed on Th2 lymphocytes, CRTH2, is a cognate receptor for prostaglandin (PG) D(2) and, in humans, is suggested to play a functional role in Th2-dependent allergic inflammation. While peripheral blood leukocytes expressing high levels of surface CRTH2 have been detected in disease, little is known of the functional significance of CRTH2 in disease etiology. We have utilized a Th2-dependent murine model of FITC-induced contact hypersensitivity to assess the role, if any, CRTH2-PGD(2) may play in the elicitation or maintenance of such pathobiology. Expression of both PGD(2) and CRTH2 in lesional skin was paralleled by the release of the chemoattractants LTB(4) and the chemokine KC, as well as a profuse dermal neutrophilic and eosinophilic infiltrate, closely paralleling the acute inflammatory pathology observed in human atopic dermatitis. A small molecule CRTH2 antagonist, but not a selective PGD(2)R (DP) receptor antagonist, was able to completely abrogate these responses. Inflammatory cascades mediated by CRTH2 ligation may therefore represent an important early step in the elicitation and maintenance of Th2-dependent skin inflammation.

Topics: Animals; Carbazoles; Chemokine CXCL1; Chemokines; Chemokines, CXC; Cytokines; Dermatitis, Allergic Contact; Dermatitis, Atopic; Eosinophils; Female; Inflammation; Leukotriene B4; Mice; Mice, Inbred BALB C; Neutrophil Activation; Neutrophils; Platelet Aggregation Inhibitors; Prostaglandin D2; Receptors, Immunologic; Receptors, Prostaglandin; Signal Transduction; Sulfonamides; Th2 Cells

Although clinical evidence has suggested that dysregulated fatty acid metabolism is associated with atopic disorders, the molecular basis for such a correlation remains to be demonstrated. In the present study, we analyzed the fatty acid composition in peripheral blood cells of NC/Nga mice, a model for atopic dermatitis (AD). We found that arachidonic acid significantly accumulated in mice with the AD manifestation. In addition, the leucotriene B4-releasing ability upon calcium ionophore A23187 stimulation was potentiated in blood cells. An arachidonic acid accumulation was not apparent in the non-atopic BALB/c strain, but was still observed in healthy NC/Nga mice fed under specific pathogen-free conditions. These results indicate that a disturbed fatty acid metabolism in NC/Nga mice was not a trigger factor for their dermatitis development.

Topics: alpha-Linolenic Acid; Animals; Arachidonic Acid; Blood Cells; Calcimycin; Dermatitis, Atopic; Disease Models, Animal; Fatty Acids; Humans; In Vitro Techniques; Ionophores; Leukotriene B4; Male; Mice; Mice, Inbred BALB C; Mice, Mutant Strains

The role of inflammatory mediators in the pathogenesis and pathophysiology of skin diseases is now widely accepted. We analysed the profiles of inflammatory mediators in normal, sensitive (past history of eczema, but currently patch test negative) and diseased (psoriasis and eczema) skin types to identify the patterns associated with various degrees of inflammatory dermatoses. Compared with normal skin, prostaglandin E2 was increased approximately 3.8-fold (p<0.0002) and 4.7-fold (p<0.0001) in suction blister fluids from sensitive and diseased skin types, respectively. Leukotriene B4 and interleukin-1alpha showed no differences between normal and sensitive skin types. However, in lesional skin from psoriasis and eczema patients, leukotriene B4 was increased approximately 6.6-fold (p<0.0001), whereas interleukin-1alpha was decreased approximately 3.1-fold (p<0.001). Interleukin 6 and tumour necrosis factor-alpha could not discriminate between skin types. We conclude that only prostaglandin E2 showed a significant stepwise increase on progression from normal through sensitive and inflammatory skin diseases. Levels of leukotriene B4 and interleukin-1alpha were also indicative of disease state and may be important in the pathophysiology of these conditions.

Topics: Adult; Dermatitis, Atopic; Dinoprostone; Disease Progression; Eczema; Humans; Immunoenzyme Techniques; Inflammation Mediators; Interleukin-1; Interleukin-6; Leukotriene B4; Middle Aged; Psoriasis; Skin; Tumor Necrosis Factor-alpha

The mediators produced from a type I allergic reaction have not yet been able to explain the pathogenesis of atopic dermatitis (AD).. The purpose of this study was to elucidate the involvement of leukotriene (LT) B4 produced from a type I allergic reaction in the pathogenesis of AD.. The release of LTB4 was measured both in vitro, in passively sensitized and antigen-challenged human skin slices, as well as in vivo, in skin chambers on patients with AD.. LTB4 was released from in vitro human skin by stimulation of the antigen (54.9 +/- 14.6 pg/g wet weight of skin by antigen challenge and 28.0 +/- 11.1 pg/g in control skin, P <.002). Antigen-specific release of LTB4 and histamine was also observed in vivo in nonlesional skin from the patients with AD by using the skin chamber technique.. LTB4 release during type I allergic reaction in human skin has been determined in vitro. The released LTB4 possibly contributes to cellular response at the acute inflammatory lesion of AD.

Topics: Adolescent; Adult; Allergens; Animals; Chemotaxis, Leukocyte; Child; Dermatitis, Atopic; Dust; Female; Histamine Release; Humans; Leukotriene B4; Male; Middle Aged; Mites; Neutrophils; Prostaglandin D2; Skin

Clinical factors and data from recent cases of atopic dermatitis (AD) (with or without ocular complications) and non-AD cases were examined to evaluate the mechanism of atopic ocular complications.. IgE-RAST for eight allergens including rice, egg, and mite and serum total IgE were measured in 216 patients with AD (70 ocular type, 146 non-ocular type) and 69 non-AD individuals. Tear histamine and leukotriene B4 (LTB4) levels were also measured.. The serum levels of IgE were significantly increased in AD patients with ocular complications compared with those without ocular complications. The positive rates of IgE-RAST for rice and wheat were significantly higher in ocular type AD than in non-ocular type AD. In ocular type AD, serum IgE was significantly increased in patients with cataract compared with that in those without cataract. Tear histamine and LTB4 levels in AD patients with ocular complications showed significant elevations compared with those in patients with pure AD and controls.. These results suggest that ocular type AD belongs to the most severe end of the spectrum of AD, and that some food antigens may contribute to the pathogenesis of severe AD resulting in ocular complications.

Topics: Adolescent; Adult; Allergens; Antibodies, Anti-Idiotypic; Child; Child, Preschool; Dermatitis, Atopic; Eye Diseases; Female; Histamine; Humans; Immunoglobulin E; Leukotriene B4; Male; Middle Aged; Tears

In this study we investigated the effect of LTB4 antagonist on eosinophil infiltration in skin and gut late phase response (LPR) in OVA-sensitized BALB/c mice. The eosinophil infiltrations to skin and gut induced by skin and oral challenge reached a peak at 12 h and 6 h after the challenge, respectively. Intraperitoneal administration of LTB4 antagonist (ONO-4057) before the challenge significantly inhibited eosinophil infiltrations to the skin and gut by 53.3% and 73.7%, respectively (p < 0.05). Next, we investigated the effect to that by PAF antagonist (ONO-6240) and anti-IL-5 mAb in the skin system. OVA-induced eosinophil infiltration at 12 h after intracutaneous challenge was significantly inhibited by peritoneal administration of anti-IL-5 mAb before the challenge by 89.6% (p < 0.05), but not by that of PAF antagonist. Our results demonstrated the inhibitory effect of LTB4 antagonist on eosinophil infiltration in skin and gut LPR, suggesting the potency of LTB4 antagonist for treatment of skin lesion and food allergy in atopic dermatitis considered to be associated with LPR.

Topics: Animals; Cell Movement; Dermatitis, Atopic; Eosinophils; Female; Immunization; Immunosuppressive Agents; Intestines; Leukotriene B4; Mice; Mice, Inbred BALB C; Ovalbumin; Phenylpropionates; Platelet Activating Factor; Skin; Thiazoles

The ex vivo release of leukotrienes B4 (LTB4) and C4 (LTC4) from the leukocytes of children with atopic dermatitis (AD) was evaluated after stimulation with Ca-ionophore and opsonized zymosan and compared with that of control children of similar ages. The blood eosinophil counts and total serum IgE levels in AD children were significantly higher than those in control children. The production of LTC4, but not LTB4, was significantly higher in AD children than in control children. There was a significant correlation between the relative blood eosinophil count and LTC4 generation after stimulation with both Ca-ionophore and opsonized zymosan in all subjects. Calculations of the amount of LTC4 produced per eosinophilic cell showed that there was no significant difference between cells from AD children and control children in terms of their ability to produce LTC4. These findings suggest that the enhanced LTC4 generation is due to increased numbers of eosinophils rather than to enhanced releasability of these cells.

Topics: Adolescent; Calcimycin; Child; Child, Preschool; Dermatitis, Atopic; Eosinophils; Female; Humans; Leukocyte Count; Leukocytes; Leukotriene B4; Leukotriene C4; Male; Zymosan

Eosinophils are implicated in the pathogenesis of a variety of allergic inflammatory diseases such as asthma. Several substances have been shown to be chemotactic for eosinophils in vitro, but the inflammatory mediators involved in the accumulation of eosinophils in vivo are as yet unidentified. In this study we have developed a system to measure the accumulation of 111In-eosinophils in guinea-pig skin in vivo. Horse serum-induced guinea-pig peritoneal eosinophils were radiolabelled with 111In and injected intravenously into recipient animals. 125I-albumin was also injected intravenously in order to measure local oedema formation simultaneously. A range of putative mediators was injected intradermally and responses measured for up to 2 hr. Of the mediators tested, guinea-pig C5a des Arg in zymosan-activated plasma was the most active. Recombinant human C5a (rHC5a) was also highly active, but less than the guinea-pig material. C5a des Arg in maximally activated plasma induced a 1500% increase in eosinophil accumulation, while rHC5a (10(-10) mol dose) induced a 600% increase. Platelet-activating factor (PAF) and leukotriene B4 (LTB4) were also tested for comparison. With respect to 111In-eosinophil accumulation, the order of potency of the mediators tested was as follows: guinea-pig C5a des Arg greater than LTB4 greater than PAF. In contrast, the order of potency of the mediators with respect to oedema formation was: PAF greater than guinea-pig C5a des Arg greater than LTB4. The techniques described will facilitate analysis of the mechanisms involved in eosinophil accumulation in defined inflammatory reactions.

Topics: Albumins; Animals; Cell Movement; Complement C5a; Dermatitis, Atopic; Eosinophils; Female; Guinea Pigs; Indium Radioisotopes; Leukotriene B4; Platelet Activating Factor; Recombinant Proteins; Skin; Zymosan

Column chromatography followed by RIA was used to measure the blood plasma content of arachidonic acid metabolites (leukotrienes C4, B4, C4/D4/E4, prostaglandins F2 alpha, E2, 6-keto-prostaglandin F1 alpha, thromboxane B2) in 146 children aged 6 months to 14 years with atopic dermatitis. The data obtained were compared to the healthy children's parameters. The majority of the patients manifested activation of the system of arachidonic acid metabolism. The intensity of changes in the content of eicosanoids was found to depend on the clinical pattern and spreading of skin lesions.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Arachidonic Acids; Child; Child, Preschool; Dermatitis, Atopic; Dinoprost; Dinoprostone; Humans; Infant; Leukotriene B4; SRS-A; Thromboxane B2

Propositions about an abnormal fatty acid metabolism in atopic dermatitis patients prompted us to compare the phospholipid fatty acid composition and LTB4 release of neutrophils from 15 atopic dermatitis patients, as well as the adipose tissue triglyceride fatty acid composition, to that of 15 healthy controls matched by age, gender, and smoking habits. We found no differences in the tissue fatty acid composition between the two groups. The release of leukotriene B4 from Ca-ionophore-stimulated neutrophils in patients was on the average only 42% (p less than 0.001) of that measured in the control group, despite the very similar arachidonic acid contents of these cells. Our study does not support the assumption of an abnormal fatty acid desaturation in atopic dermatitis patients. Rather, the capacity to release and/or convert arachidonic acid into leukotrienes in neutrophils appears to be affected by this disease.

Topics: Adipose Tissue; Adult; Body Mass Index; Chromatography, Gas; Dermatitis, Atopic; Energy Metabolism; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Leukotriene B4; Male; Neutrophils; Phospholipids; Reference Values; Triglycerides

Employing a radioimmunoassay, de-proteinated suction blister fluid from 12 patients with active atopic dermatitis appeared to contain higher levels of the pro-inflammatory and immunomodulatory mediator leukotriene B4 (LTB4) than suction blister fluid from 12 non-atopic individuals. Indirect support for the identity of the mediator was obtained by HPLC of pooled samples. Nylon wool enriched T cells from six patients with atopic dermatitis and six non-atopic people preincubated with LTB4 (10(-10) M - 10(-8) M) expressed no statistically significant suppression in co-culture with mitogen stimulated autologous mononuclear cells, and there was no difference between atopic and non-atopic T cells in this respect. In contrast, LTB4 induced a dose-dependent reduction in the percentage of phenotypic Leu 2a (suppressor) cells leading to an increased helper/suppressor ratio in five atopic patients that was not observed in five non-atopics. Elevated skin levels of LTB4 may initiate or amplify dermal inflammation, and abnormal T cell response to the mediator may account for the increased helper/suppressor ratio characteristic of patients with atopic dermatitis.

Topics: Adult; Blister; Chromatography, High Pressure Liquid; Dermatitis, Atopic; Humans; Leukotriene B4; Radioimmunoassay; Skin; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The biochemical events leading to atopic dermatitis (AD) are unknown. Certain eicosanoids derived from arachidonic acid are potent mediators of skin inflammation and modulators of certain T-lymphocyte activities. The purpose of the present study was to determine whether eicosanoids are present in biologically active concentrations in the skin of adult patients with AD. The levels of the cyclooxygenase product, prostaglandin E2 (PGE2) and the lipoxygenase products, leukotriene B4 (LTB4), 12- and 15-hydroxyeicosatetraenoic acid were determined in biopsy specimens obtained by keratome from lesional, perilesional, and clinically unaffected skin of patients with AD. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassays. Eicosanoid levels were at the same level in normal skin and in uninvolved skin of AD. Compared with uninvolved skin, both lesional and perilesional skin contained markedly elevated concentrations of PGE2 and LTB4: PGE2, 97.2 +/- 15.6 ng/gm of lesional skin and 128.3 +/- 27.2 ng/gm of perilesional skin; LTB4, 5.2 +/- 1.6 ng/gm of lesional skin and 3.2 +/- 0.6 ng/gm of perilesional skin. Compared with uninvolved skin, the levels of 12- and 15-hydroxyeicosatetraenoic acid were elevated sevenfold and elevenfold, respectively, in lesional skin, but did not reach biologically active concentrations. The results demonstrate that the inflammatory mediators PGE2 and LTB4 are present in lesional skin of atopic subjects in biologically active concentrations. Because these mediators are able to induce cutaneous inflammation and to modulate cellular immunity, they may be involved in the biochemical processes leading to AD.

Topics: Adolescent; Adult; Chromatography, High Pressure Liquid; Dermatitis, Atopic; Dinoprostone; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Middle Aged; Radioimmunoassay; Skin

Involved skin in atopic eczema contains elevated levels of the 5-lipoxygenase metabolite of arachidonic acid, leukotriene B4. In addition, leukocytes of atopic eczema patients produce increased amounts of eicosanoids upon immunological challenge. These facts and the biological effects of eicosanoids suggest their involvement in the pathogenesis of cutaneous inflammation in atopic eczema, and may provide a new target for pharmacological treatment of this disease.

Topics: Dermatitis, Atopic; Eicosanoic Acids; Humans; Leukotriene B4; Skin

Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in psoriatic lesions. Elevated concentrations of the chemoattractant eicosanoid leukotriene B4 (LTB4) are present in psoriatic skin. Its chemotactic activity is mediated via high affinity receptors on PMNL. The goal of our work was to ascertain whether PMNL infiltration in psoriasis can be accounted for by functional abnormalities of the circulating PMNL due to alterations in the LTB4 receptor density or affinity (or both). No significant difference was found between patients with psoriasis, healthy controls and patients with another inflammatory dermatosis (atopic eczema) with regard to the binding parameters of LTB4 receptors on PMNL. Our findings suggest that PMNL accumulation in psoriatic skin may be the result of an excess of cutaneous chemoattractant rather than the increased readiness of psoriatic PMNL to migrate towards LTB4 due to altered LTB4 receptor density or affinity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermatitis, Atopic; Female; Humans; Kinetics; Leukotriene B4; Male; Middle Aged; Neutrophils; Protein Binding; Psoriasis; Receptors, Immunologic; Receptors, Leukotriene B4

Purified peripheral blood monocytes isolated from patients with atopic dermatitis (AD) and from nonallergic normal donors were compared for their abilities to release leukotriene C4 (LTC4), leukotriene B4 (LTB4) and beta-glucuronidase in response to challenge with aggregated immunoglobulins or anti-immunoglobulins. The relationship between mediator release and the number of monocytes that formed rosettes with immunoglobulin-coated indicator cells was examined. Patients with AD had twice as many IgA- and three times as many IgE-rosetting monocytes as normal donors (48 +/- 12% versus 27 +/- 10% and 40 +/- 15% versus 14 +/- 3%, respectively), and yet the amounts of IgA- and IgE-induced LTC4 released were similar for both groups. This apparent discrepancy did not result from a decreased capacity for arachidonate metabolism via the C5-lipoxygenase pathway, since stimulation of monocytes from patients and normal donors with the calcium ionophore A23187 induced similar amounts of LTC4 and LTB4 release (LTC4, 3.0 +/- 1.7 versus 3.0 +/- 1.0 ng/10(6) cells; LTB4, 5.3 +/- 0.7 versus 5.2 +/- 0.5 ng/10(6) cells, respectively). In addition, aggregated IgG-induced LTC4 release by monocytes of both groups was similar, concomitant with an equivalent number of IgG-rosetting cells. Determination of cytophilically bound IgG and IgE by flow cytometry demonstrated that monocytes from atopic patients had more IgG bound than monocytes from normal donors. Similar amounts of IgE were detected on most monocytes from both groups, despite the higher serum IgE levels of patients. However, approximately 3% to 8% of monocytes from atopic but not normal donors stained brightly for IgE, suggesting that relatively large amounts of cytophilic IgE were bound to a small percentage of the patients' monocytes. Challenge of monocytes with anti-IgE or anti-IgG induced release of similar amounts of LTC4 for both groups, despite the presence of more cytophilic IgG on monocytes from atopic donors. These data indicate that monocytes from patients with AD release LTC4 and LTB4 in response to challenge with aggregated IgE or anti-IgE, as well as aggregated IgG, IgA, and anti-IgG. However, under our in vitro conditions, stimulation of patients' monocytes with aggregated IgA or IgE was not associated with increased mediator release, despite higher percentages of IgA- and IgE-rosetting cells compared to normal donors.

Topics: Antigens, Differentiation; Antigens, Differentiation, B-Lymphocyte; Calcimycin; Dermatitis, Atopic; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin Fab Fragments; Immunoglobulin G; Leukotriene B4; Macromolecular Substances; Male; Monocytes; Receptors, Fc; Receptors, IgE; Receptors, IgG; Rosette Formation; SRS-A

In 15 patients with atopic dermatitis (AD) and without concomitant viral or bacterial infections, chemotaxis, superoxide-anion (O2-) generation, and beta-glucuronidase release of purified monocytes (MO) and neutrophils (PMN) were determined. Defined receptor-dependent stimulators (i.e., N-formyl-methionyl-leucyl-phenylalanine, C5a, and leukotriene B4, as well as native and opsonized zymosan particles) were used for phagocyte stimulation. PMN functional activities in response to the stimuli tested were found to be normal in patients with AD and without infections. MO from these patients revealed a slight enhancement of O2- production after stimulation with opsonized zymosan and a small increase of N-formyl-methionyl-leucyl-phenylalanine-induced chemotaxis. Other MO functions tested were within the normal range. However, investigations of MO and PMN functions during the course of concomitant bacterial infections of three patients with AD demonstrated striking alterations of cellular responsiveness. These changes ranged from enhanced to decreased phagocyte functions, depending on the activity of the infectious disorder. Chemotaxis of PMN and MO was depressed around the third day after onset of the infectious disease. In the beginning of infection, there was a decreased O2- generation and beta-glucuronidase release in PMNs. In MOs, both parameters were enhanced. The results of these investigations provide evidence that functional abnormalities of phagocytes observed in patients with AD are sequelae of concomitant skin infections and not signs of an intrinsic defect present in MOs and PMNs.

Topics: Adolescent; Adult; Bacterial Infections; Chemotaxis, Leukocyte; Complement C5; Complement C5a; Dermatitis, Atopic; Female; Follow-Up Studies; Glucuronidase; Humans; Immunoglobulin E; Leukotriene B4; Longitudinal Studies; Male; Middle Aged; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Phagocytosis; Superoxides

The releasability of arachidonic acid-derived inflammatory mediators (eicosanoids) from peripheral blood leukocytes has been tested in patients with atopic eczema and healthy, non-atopic controls. Spontaneous and stimulated release of prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and leukotriene C4 (LTC4) has been measured after challenge of cells with various concentrations of anti-IgE, Ca-ionophore A23187 and C5a. The maximal stimulation of cells with Ca-ionophore resulted in the generation of high amounts of all eicosanoids, which was essentially equal in both atopic and control groups. On the other hand, enhanced spontaneous and stimulated eicosanoid release was noted after immunological challenge using C5a and anti-IgE in the atopic eczema group. Thus, our data support the hypothesis of enhanced releasability of inflammatory mediators in atopic eczema.

Topics: Adolescent; Adult; Aged; Antibodies, Anti-Idiotypic; Arachidonic Acids; Calcimycin; Child; Complement C5; Complement C5a; Dermatitis, Atopic; Dinoprostone; Female; Humans; Immunoglobulin E; Leukocytes; Leukotriene B4; Male; Middle Aged; Prostaglandins E; SRS-A

Peripheral blood neutrophils and eosinophils from 70 patients and controls were studied for their in vitro chemotactic and chemokinetic responses towards synthetic leukotriene B4 (LTB4), 20-OH-LTB4 and 20-COOH-LTB4. All three factors induced chemotaxis and chemokinesis of cells. 20-OH-LTB4 was always less and 20-COOH-LTB4 even less active than the parent compound. Cells from patients with atopic eczema and T cell lymphoma moved less than cells from normal controls or from patients with psoriasis. In the presence of LTB4, 20-OH-LTB4 and buffer alone, more eosinophils than neutrophils moved to the lower side of the filter, while this did not occur with platelet activating factor as chemoattractant. Studies of neutrophil and eosinophil chemotaxis in the presence of LTB4 should therefore always take into account a high variability of the quantitative response which is donor and disease dependent.

Topics: Chemotaxis, Leukocyte; Dermatitis, Atopic; Eosinophilia; Eosinophils; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lymphoma; Neutrophils; Psoriasis

Since the biochemical events leading to cutaneous inflammation in atopic dermatitis and psoriasis are unknown, we studied the levels of arachidonic acid-derived mediators of inflammation as well as histamine in the suction blister fluid obtained from lesional and nonlesional skin of patients with these dermatoses. Mediator levels were determined radioimmunologically. Skin from healthy controls and uninvolved skin from patients contained very low or unmeasurable levels of the 5-lipoxygenase metabolite of arachidonic acid, leukotriene (LT) B4. In contrast, higher levels of LTB4-like immunoreactivity were detected in suction blister fluid from lesional atopic dermatitis skin, and even higher concentrations occurred in psoriasis lesions. LTB4-like immunoreactivity from atopic dermatitis suction blister fluid cochromatographed on reverse-phase high-pressure liquid chromatography with authentic LTB4, thus excluding cross-reaction of the LTB4-antibody with arachidonic acid or monohydroxyeicosatetraenoic acids. In contrast, suction blister concentrations of the cyclooxygenase metabolite of arachidonic acid prostaglandin (PG) E2 showed no significant differences between lesional and nonlesional patient skin and healthy control skin. PGD2 determined as a stable metabolite could not be detected in these samples. Histamine concentrations in lesional skin were within normal range. The elevated levels of the potent proinflammatory and immunomodulating mediator LTB4 could be involved in the pathogenesis of cutaneous inflammation in atopic dermatitis and psoriasis. In addition, they might explain the therapeutic efficiency of glucocorticosteroids, which among other actions inhibit the release of arachidonic acid from phospholipid stores by blocking the enzyme phospholipase A2. However, the specificity of disease expression in atopic dermatitis and psoriasis must be due to factors other than cutaneous LTB4 elevation.

Topics: Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Dermatitis, Atopic; Dinoprostone; Female; Histamine; Humans; Leukotriene B4; Male; Middle Aged; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Psoriasis; Skin

Topics: Acne Vulgaris; Arachidonic Acid; Arachidonic Acids; Capillary Permeability; Dermatitis, Atopic; Dermatitis, Contact; Humans; Leukotriene B4; Lipoxygenase; Lymphocytes; Phagocytes; Psoriasis; Skin; Skin Diseases; SRS-A; Urticaria

Topics: Adolescent; Adult; Aged; Dermatitis, Atopic; Female; Humans; Leukotriene B4; Male; Middle Aged; Skin

Topics: Dermatitis, Atopic; Exudates and Transudates; Humans; Leukotriene B4; Skin

In vitro monocyte chemotaxis towards leukotriene B4(LTB4) and platelet activating factor (PAF) was studied with cells from 51 patients with various inflammatory dermatoses and 12 normal volunteers. Monocytes from normal subjects responded poorly to LTB4 (10(-8)-10(-12) M) and PAF (10(-6)-10(-10) M), and cells from patients with urticaria pigmentosa and vericella were even less responsive, while monocytes from patients with severe psoriasis and atopic eczema exhibited markedly enhanced chemotaxis. These changes persisted during high dose therapy with oral steroids, but returned to normal with healing of the skin lesions. Pre-incubation of monocytes with histamine, LTB4, PAF, lymphokines or sera from patients and normal controls did not result in enhanced chemotaxis of the cells. The chemotactic activity of monocytes did not correlate with that of neutrophils in the same patients (r = 0.08). Altered monocyte chemotaxis in patients with inflammatory dermatoses is therefore a reversible process that is related to the severity of the cutaneous inflammation but is not limited to a specific disease.

Topics: Adolescent; Adult; Cells, Cultured; Chemotaxis, Leukocyte; Child; Dermatitis; Dermatitis, Atopic; Dose-Response Relationship, Immunologic; Female; Humans; Leukotriene B4; Male; Monocytes; Platelet Activating Factor; Psoriasis; Urticaria