Inhibition of neutrophil responses by cyclosporin A. An insight into molecular mechanisms

S. Spisani, E. Fabbri, M. Muccinelli, A. Cariani, L. Barbin, F. Trotta, L. Dovigo
2001 Rheumatology  
Objective. Cyclosporin A (CsA) is an effective agent in rheumatoid arthritis (RA), slowing joint damage progression. Its therapeutic effect on T lymphocytes has been studied extensively, but there is little information available about neutrophils, the cells responsible for a substantial proportion of in¯ammation. A study was performed to investigate the in vitro effects of CsA on neutrophil functions triggered by several agonists and determine whether the drug could counteract the binding of
more » ... myl-methionyl-leucyl-phenylalanine (f MLP) to its receptor anduor modulate changes in the intracellular Ca 2+ concentration ([Ca 2+ ] i ). Methods. CsA was added to neutrophils 5±50 min before the incubation steps for neutrophil function assays (chemotaxis, superoxide anion production, lysozyme release), calcium measurements and receptor binding experiments. Results. CsA appeared to be particularly effective in lowering chemotaxis, superoxide anion production and lysozyme release induced by different agonists. However, it did not signi®cantly affect either basal or agonist-stimulated neutrophil [Ca 2+ ] i and the interaction between f MLP and its receptor. Conclusions. Because of its in vitro inhibition of neutrophil functions, CsA appears to have considerable potential as an anti-in¯ammatory drug. Moreover, as it is also a potent immunosuppressive agent, it may reduce the progression of joint damage in RA. More work remains to be done to clarify the molecular mechanism of CsA action on neutrophils.
doi:10.1093/rheumatology/40.7.794 pmid:11477284 fatcat:fnbxwlefhrg3hf7v4uierx5jh4