Correction of an in vitro immunoregulatory defect in atopic subjects by the immunostimulating drug fanetizole mesylate (CP-48,810).
The effect of Fanetizole mesylate or CP-48,810, a new immunostimulating drug, on suppressor cell function and IgE synthesis in vitro was evaluated in atopic patients with allergic rhinitis and/or asthma and eczema. In the absence of the drug, histamine (10(-3)M) stimulated blood mononuclear cells from 23 atopic patients suppressed concanavalin A-induced lymphocyte proliferation by a mean (+/- S.E.M.) of 9.3% +/- 3.5 (compared to 25.1% +/- 2.7 for histamine stimulated mononuclear cells from non-atopic controls). The addition of the drug (2.5 X 10(-4)M) in vitro significantly increased histamine suppressor cell activity of atopic patients to 26.6% +/- 3.9 (compared to 24.7% +/- 2.8 for control cells in the presence of the drug). In order to determine a possible mechanism through which CP-48,810 might enhance histamine-induced suppressor activity, we examined the effects of the drug on the production of histamine-induced suppressor factor (HSF) by lymphocytes and the production of prostaglandin E2 by blood monocytes in the presence of HSF. Supernatants generated from histamine (10(-4)M) stimulated patient lymphocytes caused a 9.0% +/- 1.8 suppression of concanavalin A-induced lymphocyte proliferation (compared to 25.0% +/- 3.1 caused by supernatants from normal subjects). If the drug (2.5 X 10(-4)M) was added at the beginning of culture, HSF activity in supernatants derived from atopic lymphocytes increased significantly to 20.2% +/- 1.8 (compared to 23.3% +/- 3.9 for drug treated control supernatants). Prostaglandin E2 production by atopic monocytes exposed to HSF was less than that of normal monocytes in the absence of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D003208:Concanavalin A / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000276:immunology; D015232:Dinoprostone; D004485:Eczema / Q000276:immunology; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011458:Prostaglandins E / Q000096:biosynthesis*; D012220:Rhinitis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013844:Thiazoles / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D011458:Prostaglandins E; D013844:Thiazoles; D003208:Concanavalin A; D007073:Immunoglobulin E; D006632:Histamine; C041551:fanetizole; D015232:Dinoprostone