Tachykinin activation of human monocytes from patients with rheumatoid arthritis: in vitro and ex-vivo effects of cyclosporin A

Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to preferentially interact with substance P (SP), neurokinin A (NKA) and neuro kinin B (NKB), respectively. We previously demonstrated that NK1 and NK2 re ceptors are present on human monocytes, SP and NKA inducing superoxide anio n production and tumor necrosis factor- alpha (TNF-alpha) mRNA expression. NK2 receptor stimulation also triggered an enhanced respiratory burst in mo nocytes isolated from rheumatoid arthritis (RA) patients. This study was ai med to evaluate the in vitro and ex-vivo effects of cyclosporin A (CsA) on tachykinins-evoked TNF-alpha release from monocytes of healthy donors and R A patients. CsA (100 ng/ml) potently inhibited phorbol ester- and tachykini n-evoked TNF-alpha secretion. In RA patients treated with CsA (Sandimmun(R) Neoral(R)) 2.5 mg/kg/die, a significant time-dependent reduction in TN F-o r secretion from monocytes was measured. This may contribute to the CsA the rapeutic activity in RA. (C) 2001 Harcourt Publishers Ltd.