A Study on the effect of cepharanthin, a biscoclaurine alkaloid, on enhancement of mitogen-induced histidine decarboxylase activity in mice spleens and the effect of histamine on the production of cytokines

Abstract

The effect of cepharanthin on the enhancement of mitogen-induced histidine decarboxylase (HDC) activity in mice spleens and the effect of histamine on the production of cytokines were investigated. Cepharanthin enhanced LPS-induced HDC activity in normal mice spleens and also enhanced it in genetically T cell-deficient nude mice spleens and T and B cell-deficient scid mice spleens. Therefore, cepharanthin can exert its effect on macrophages without T cells or B cells. Cepharanthin enhanced LPS-induced cytokine production by macrophages. Histamine induced cytokine production and enhanced LPS-induced cytokines production by macrophages. However, diphenhydramine and cimetidine, histamine receptor antagonists, did not block this process. Alpha-fluoromethylhistidine, a suicide inhibitor of HDC, suppressed LPS-induced cytokine production. These results suggest that cytokine production by macrophages is regulated by both histamine added exogenously and histamine induced by macrophages themselves and that hista mine participates in enhancement of cytokine production by cepharanthin. © 1995, The Japanese Pharmacological Society. All rights reserved.