Effect of cyclosporin A on inflammatory cytokine production by human alveolar macrophages

Abstract

Cyclosporin A (CsA) is an immunomodulator drug that has been used in the treatment of several types of advanced pulmonary interstitial disease. This beneficial effect occurs mainly in circumstances in which alveolitis due to CD4 lymphocytes is absent, suggesting that CsA acts on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by human alveolar macrophages (AMs). Human AMs were collected by bronchoalveolar lavage from four control subjects and 13 patients with interstitial lung disease. Purified human AMs were incubated with different concentrations of CsA (200, 20 and 2 ng ml(-1)) in the presence or absence of lipopolysaccharide (LPS). Interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in supernatants 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 ml(-1). However, none of the different concentrations of CsA modified basal secretion of IL-1 beta nor IL-6. By contrast, a lower concentration of CsA (2 ng ml(-1)) inhibits LPS-stimulated secretion of all inflammatory cytokines. It is concluded that CsA exerts a modest effect on inflammatory cytokine production by human AMs.