ABSTRACT
Our studies target alternative/adjuvant therapies in allergic diseases, able to qualitatively/quantitatively modify cytokine profiles produced by both CD4+ T-cell subsets (mainly Th1 and Th2) and B-cells, macrophages, etc. Current investigations aim to identify compounds capable to down-regulate IL-10 as an exponent of Th2 cell function and, consequently, to up-regulate Th1 cytokine levels. Experiments on ten allergic asthmatic patients and ten healthy subjects as control were performed. Cytokine production, triggered in PBMCs culture systems by PHA, was modulated with Indomethacin, a non-steroidal anti-inflammatory drug and IL-10 was measured in 24 hours culture supernatants. According to our experimental data, IL-10 level of asthmatic patients' PBMCs in the resting state is not significantly different from control. PHA-activated PBMCs from asthmatic patients do not display significantly higher IL-10 levels than the normal subjects. The results obtained up-to-date reveal the fact that Indomethacin strongly down-regulates IL-10 levels in PBMCs cultures, in both asthmatic allergic patients and healthy subjects. It is obvious that the inhibitory effect of Indomethacin on IL-10 released by PBMCs is higher in the case of allergic asthmatic patients. The results obtained in this study demonstrate that Indomethacin is a possible therapeutic candidate in allergic asthma.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Asthma/drug therapy , Hypersensitivity, Immediate/drug therapy , Indomethacin/pharmacology , Interleukin-10/biosynthesis , Leukocytes, Mononuclear/drug effects , Adolescent , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asthma/immunology , Child , Female , Humans , Hypersensitivity, Immediate/immunology , Indomethacin/therapeutic use , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Male , Middle AgedABSTRACT
To quantify objectively the comparative potencies of the antihistamines, loratadine and cetirizine, we determined the dose that inhibits histamine-induced skin reactions by 50% of the maximum response (ED50) for each drug. Cetirizine at 2.5, 5 or 10 mg, loratadine at 10, 20 or 40 mg or placebo were given to 14 healthy female subjects in a randomized double-blind crossover design. Inhibition of the wheal and flare response to the histamine prick test (10, 100 and 500 mg/ml) was evaluated. Depending on the histamine concentrations, the ED50s for wheals were in the ranges 4.3 - 4.7, 2.1 - 2.2 and 1.7 - 1.9 mg cetirizine, 2, 4 and 6 h after dosing, respectively. For loratadine, the ED50 for wheals were in the ranges 35.6 - > 40, 9.1 - 24.1 and 9.1 - 13.9 mg, 2, 4 and 6 h after dosing, respectively. Calculation of the ED50 demonstrated that, on average, cetirizine is seven to nine times more potent than loratadine at inhibiting wheal and flare reactions.
