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Notes: Background: The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU).Methods: Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine.Results: For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P 〈 0.0001; A vs. B2, P 〈 0.0001; A vs. C1, P 〈 0.0001; A vs. C2, P 〈 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P 〈 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P 〈 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients.Conclusion:  Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.

Notes: Background: Topical corticosteroids are beneficial in the treatment of allergic respiratory disorders; they exert effects on a number of cells involved in allergic inflammatory reactions. On the other hand, major histocompatibility complex (MHC)-unrestricted cytotoxicity (i.e., natural killer [NK] cell activity) may play a role in the inflammatory allergic reaction. The objective was to gain insight into the mechanisms of the therapeutic effects of fluticasone propionate (FP), an inhaled corticosteroid used in asthma and rhinitis therapy. Therefore, we evaluated the NK and lymphokine-activated killer (LAK) activity of effector cells in vitro treated or not with FP. Methods: Evaluations were made on peripheral blood mononuclear cells (PBMNCs), obtained from healthy volunteers (n=10) and from asthmatic atopic subjects (n=10) with allergy to Parietaria. Results: Asthmatic patients had significantly increased NK activity (P=0.0008), and interleukin (IL)-2- (P=0.0005) and interferon (IFN)-α-induced LAK activities (P=0.0005). In both groups, FP 10−7 M significantly reduced NK activity (P〈0.0001), IL-2-induced LAK activity (P〈0.0001), and IFN-α-induced LAK activity (P〈0.0001). Similar results were obtained
with FP 10−8 M. Conclusions: Since MHC-unrestricted cytotoxicity has been implicated in the development of allergen-induced eosinophilic airway inflammation, inhibition of NK and LAK activity by FP may contribute to the steroid therapeutic effect in asthma.