Regulation of IL-4 and IL-5 secretion by histamine and PGE2.

Abstract

This study was designed to study the effects of autacoids on IL-4 and IL-5 secretion. IL-4 and IL-5 are secreted by TH2 cells. TH2 cells were generated by the culture of peripheral blood lymphocytes from atopic individuals in the presence of ragweed or dustmite antigen. The cloned TH2 lymphocytes were then stimulated with PMA (10 ng/ml) and alpha-CD3 (50 ng/ml) in the presence and absence of histamine (10(-4) - 10(-8)M) and PGE2 (10(-6) - 10(-8)M) for 48 hours. Other cAMP elevating agents were used as control. The supernatants were then assayed for the presence of IL-4 and IL-5 by ELISA. Both histamine and PGE2 suppressed the secretion of IL-4 in a dose dependent manner. Other cAMP elevating agents did not affect IL-4 secretion. In contrast, histamine upregulated the secretion of IL-5, whereas the effects of PGE2 on IL-5 secretion were not conclusive. Chloride channels have been implicated in the secretory processes. The effects of a chloride channel blocker, DIDS, were studied on histamine-induced suppression of IL-4 secretion. DIDS (10(-7) - 10(-12)M) abrogated the inhibitory effects of histamine on IL-4 secretion. The observations suggest that histamine may inhibit IL-4 secretion via activation of chloride channels.