Effect of cyclosporin A on inflammatory cytokine production by U937 monocyte-like cells

CYCLOSPORIN A (CsA) is an immunosuppresor drug that has been used in the tr eatment of several types of inflammatory diseases. In some of them the inhi bition of T-lymphocyte activation does not suitably account for the observe d beneficial effect, suggesting that CsA could act on other types of cells. The present study was undertaken to determine the effect of CsA on inflamm atory cytokine secretion by U937 monocyte cells. Undifferentiated and dimet hylsulfoxide ;(DMSO) differentiated U937 cells were incubated with differen t concentrations of CsA (200, 20 and 2 ng/mL) in the presence or absence of phorbol-myristate acetate (PMA). Interleukin-1 beta (IL-1 beta), tumor nec rosis factor-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in super natants using specific enzyme-linked immunosorbent assays. At the highest c oncentration used (200 ng/mL) CsA decreased the basal and stimulated secret ion of all the inflammatory cytokines studied in both undifferentiated and differentiated cells, with the only exception of PMA-stimulated IL-1 secret ion by undifferentiated cells. However, only basal secretion of interleukin -8 in both undifferentiated and DMSO-differentiated U937 cells was signific antly reduced by CsA at the highest concentration (200 ng/ mL). At therapeu tic concentrations in vivo, CsA exerts a predominant effect on IL-8 secreti on by human mononuclear phagocytes.