Effect of Colchicine on Lymphocyte and Monocyte Function and Its Relation to Fibroblast Proliferation in Primary Biliary Cirrhosis

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Abstract
Lymphocyte and monocyte function was investigated in eight patients with primary biliary cirrhosis and in age–matched and sex–matched controls. In three of the eight cirrhotic patients, two were in the late stage of the disease (stage III) and concanavalin A–induced suppressor cell function was markedly decreased; it returned to normal levels after 1 mo of treatment consisting of 5 mg per week of orally administered colchicine. The relative percentage of T cell subsets (CD3, CD4 and CD8) and the mean percentage of the helper and the suppressor phenotype were similar in cirrhotic patients and in controls. Basal production of interleukin–1 activity by a monocyte–enriched fraction of peripheral blood mononuclear cells of cirrhotic patients was three–fold above control values: after stimulation with endotoxin, interleukin–1 values increased tenfold above basal levels in monocyte–enriched fraction of peripheral blood mononuclear cells of both normal and cirrhotic patients. Colchicine normalized the basal production of interleukin–1 and inhibited its stimulation by endotoxin by 50%. Culture supernatants of endotoxin–stimulated monocyte–enriched fraction of peripheral blood mononuclear cells increased the proliferation of cultured human skin fibroblasts by 50%. In contrast, supernatants from stimulated monocyte–enriched fraction of peripheral blood mononuclear cells obtained from colchicine–treated patients significantly inhibited fibroblast proliferation. These findings suggest that stimulated chronic inflammatory cells may play an important role in liver fibrosis. Some of the actions of colchicine could be related to its effects on lymphocyte and monocyte function.