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.

Reduced production of histamine-induced suppressor factor (HSF) by atopic mononuclear cells and decreased prostaglandin E2 output by HSF-stimulated atopic monocytes.

To characterize the defect responsible for abnormal histamine-induced suppressor cell function observed in atopic subjects, we studied histamine-induced suppressor factor (HSF) production and augmented prostaglandin E2 production. In addition, we exogenously provided interleukin 1 to determine whether abnormal histamine-induced suppressor cell function could be corrected by this monokine. Mononuclear cells from 16 asymptomatic atopic subjects generated significantly less (p less than 0.

Augmentation of prostaglandin and thromboxane production in vitro by monocytes exposed to histamine-induced suppressor factor (HSF).

A possible mechanism to explain the suppression of mitogen-induced lymphocyte proliferation in vitro by histamine-stimulated mononuclear cells was investigated. In initial experiments, the inhibitory action of histamine-induced suppressor factor (HSF) on lymphocyte proliferation was documented to be reduced by the addition of indomethacin (1 microgram/ml). Moreover, the addition of exogeneous PGE2 (10(-7)-10(-8) M) to mononuclear cell cultures reconstituted HSF activity in the presence of indomethacin.