leukotriene-b4 and Urticaria

The leukotrienes, so named because of their initial identification in leukocyte preparations and the presence of three conjugated double bonds (a conjugated triene), are metabolites of the same polyunsaturated fatty acids (e.g., arachidonic acid) that give rise to the prostaglandins, thromboxanes, and several other families of biologically active lipids. Their potential clinical importance derives from their effects on vascular and other smooth muscle reactivity and on leukocyte function. Several leukotrienes may markedly influence the cellular and vascular responses that constitute an integral part of hypersensitivity and inflammatory reactions of the skin. Preliminary data from several laboratories have been presented that implicate a specific leukotriene in the evolution of the lesions of psoriasis.

Topics: Arachidonic Acid; Arachidonic Acids; Humans; Leukocytes; Leukotriene B4; Muscle, Smooth; Muscle, Smooth, Vascular; Psoriasis; Skin; SRS-A; Urticaria

H(1)-antihistamines are widely used in the treatment of various allergic diseases. Particularly, a cornerstone of the management of chronic idiopathic urticaria is treatment with H(1)-antihistamines. However, a few cases of H(1)-antihistamine-induced urticaria have been reported. A 34-year-old woman presented with a 4-month history of recurrent urticaria, which was prominently exacerbated by the administration of H(1)-antihistamines. The patient consented to a provocation test of fexofenadine among drugs including cetirizine and hydroxyzine, which were suspected of inducing severe symptoms in episodes. One hour after challenge with 12 mg fexofenadine (one-fifth of the therapeutic dose), a urticarial reaction rapidly developed on nearly the entire body with remarkably increased levels of plasma histamine (190 nmol/L) and plasma leukotriene B4 (150 pg/mL). In challenge tests with other antihistamines, generalized urticaria occurred 5 and 1 h after intake of 10 mg loratadine and 10 mg bepotastine, respectively, whereas challenges with chlorpheniramine, mequitazine and azelastine were all negative. Skin prick tests with H(1)-antihistamines used in the challenges were all negative, indicating that the urticarial reactions after challenges with the causative drugs might not be immunoglobulin E-mediated. Among the causative drugs in our case, cetirizine and hydroxyzine are the piperazine derivatives, whereas fexofenadine, bepotastine, ebastine and loratadine are the piperidine derivatives. The chemical structures of both derivatives are very similar. Therefore, in this case, H(1)-antihistamine-induced urticaria may have been due to cross-reactivity between metabolites of these drugs, but not to drugs before metabolization. Hypersensitivity to H(1)-antihistamines should be considered when urticarial lesions worsen after H(1)-antihistamine treatment.

Topics: Administration, Oral; Adult; Drug Eruptions; Female; Histamine; Histamine H1 Antagonists; Humans; Immunologic Tests; Leukotriene B4; Loratadine; Piperidines; Pyridines; Skin Tests; Terfenadine; Urticaria

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

The leukotriene generating capacities of ionophore stimulated human eosinophils and neutrophils were compared using specific radioimmunoassays for LTB4 and LTC4. Mixed granulocyte preparations (neutrophils and eosinophils) produced both LTB4 and LTC4 in a time-dependent fashion which was maximal at 10 and 15 min, respectively. Following the separation of eosinophils (greater than 75%) and neutrophils (greater than 90%) by metrizamide gradients, LTC4 production was predominantly from eosinophils, whereas neutrophils were the principal source of LTB4. The concentrations of leukotrienes produced by the eosinophil and neutrophil rich cell preparations were directly proportional to the concentration of ionophore. Following purification of eosinophil derived products by RP-HPLC the LTC4 immunoreactivity corresponded to the elution profile of a synthetic LTC4 marker. Furthermore, in 32 atopic subjects (21 bronchial asthmatics and 11 non-asthmatics) the amounts of LTC4 produced by unseparated leucocytes were directly proportional to the percentage of eosinophils in the total cell suspension. Preferential generation of LTB4 by neutrophils was also demonstrated by immunoreactivity of ionophore stimulated supernatants subjected to RP-HPLC, as well as by its characteristic u.v. absorbance and GC-MS profile and the ability to promote directional neutrophil locomotion (chemotaxis). These experiments support the concept that eosinophils accumulate in tissues partly as a result of the response to neutrophil derived LTB4, and that these cells contribute to the production of sulphidopeptide leukotrienes with subsequent amplification of the acute allergic response.

Topics: Adolescent; Adult; Asthma; Calcimycin; Eosinophils; Granulocytes; Humans; Leukotriene B4; Middle Aged; Neutrophils; Radioimmunoassay; Rhinitis; SRS-A; Urticaria

Topics: Albuterol; Aminophylline; Cold Temperature; Histamine Release; Humans; Leukotriene B4; Models, Biological; Psoriasis; Skin; Urticaria

Possible alterations in the release of eosinophil chemotactic leukotrienes (ECL) were studied with leukocytes from 14 patients with chronic urticaria due to pseudo-allergic reactions (PAR) and from 14 healthy volunteers. Patients tended to release less ECL, and inhibition of ECL release was more marked in the presence of cyclooxygenase and lipoxygenase inhibitors. The latter compounds did not cause ECL secretion by themselves. Increased release of lipoxygenase products of arachidonate metabolism from blood leukocytes is therefore an unlikely cause for PAR.

Topics: Chemotactic Factors; Chemotactic Factors, Eosinophil; Humans; Indomethacin; Leukotriene B4; Neutrophils; Urticaria

Intradermal injections of 1-50 pmol leukotriene B4, C4, D4 and E4, (LTB4, LTC4, LTD4 and LTE4) were performed in healthy subjects and patients with recurrent urticaria. A wheal and erythema were seen 15 minutes after injection and were most marked after LTC4 and LTD4. LTE4 also produced a wheal whereas the reaction to LTB4 did not significantly differ from the saline control. When mixed with histamine no potentiation of the wheals was noted and no significant difference in reaction was observed between the healthy controls and those with urticaria.

Topics: Drug Hypersensitivity; Erythema; Histamine; Humans; Intradermal Tests; Leukotriene B4; Leukotriene E4; Male; Skin; SRS-A; Urticaria

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