EFFECT OF CYCLOSPORINE-A ON INFLAMMATORY CYTOKINE PRODUCTION BY HUMANALVEOLAR MACROPHAGES

Cyclosporin A (CsA) is an immunomodulator drug that has been used in t he treatment of several types of advanced pulmonary interstitial disea se. This beneficial effect occurs mainly in circumstances in which alv eolitis due to CD4 lymphocytes is absent, suggesting that CsA acts on other types of cells. The present study was undertaken to determine th e effect of CsA on inflammatory cytokine secretion by human alveolar m acrophages (AMs). Human AMs were collected by bronchoalveolar lavage f rom four control subjects and 13 patients with interstitial lung disea se. Purified human AMs were incubated with different concentrations of CsA (200, 20 and 2 ng ml(-1)) in the presence or absence of lipopolys accharide (LPS). Interleukin-1 beta (IL-1 beta), tumour necrosis facto r-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in supernatant s using specific enzyme-linked immunosorbent assays. II was found that CsA inhibits basal secretion of TNF-alpha and IL-8 at 20 and 200 ng m l(-1). However, none of the different concentrations of CsA modified b asal secretion of IL-1 beta nor IL-6. By contrast, a lower concentrati on of CsA (2 ng ml(-1)) inhibits LPS-stimulated secretion of all infla mmatory cytokines. It is concluded that CsA exerts a modest effect on inflammatory cytokine production by human AMs.