Colchicine derivatives inhibit neopterin production in human peripheral blood mononuclear cells (PBMC)

Colchicine is a microtubule disrupting agent, mostly used as treatment in various kinds of inflammatory diseases such as acute familial Mediterranean fever and Behcet's disease. as well as gout. In patients with familial Mediterranean fever treatment with colchicine induces a decline of urinary neopterin concentrations which indicates a decrease of cell-mediated immune activation. In this study, we investigated a potential effect of colchicine on the T cell/macrophage system iii vitro. The human myelomonocytic cell line THP-1 and PBMC were treated with colchicine or the colchicine derivative, colcemide, in the presence or absence of 250 U/ml interferon-gamma (IFN-gamma) or 10 mu g/ml lipopolysaccharide (LPS) for 48 h or 96 h. Colchicine and colcemide increased neopterin/protein production in unstimulated THP-1 cells, but no such effect was apparent in cells stimulated with IFN-gamma. By contrast, when PBMC were treated with colchicine or colcemide a significant reduction in neopterin formation was evident in cells without and with prestimulation by IFN-gamma or LPS. In parallel, reduced production of IFN-gamma was observed in PBMC. These data suggest that colchicine and colcemide are able to inhibit T cell activation within the cellular immune response.