IMPAIRED IL-1-BETA-INDUCED NEUTROPHIL ACCUMULATION IN TACHYKININ NK1 RECEPTOR KNOCKOUT MICE

Tachykinin NK1 receptors play an important role in the development of neurogenic inflammatory responses. We have used the murine air-pouch m odel to investigate whether the neurogenic component of the cellular i nflammatory response to interleukin-1 beta (IL-1 beta, 10 ng into the air-pouch) is altered in NK1 receptor knockout mice compared to wild t ype controls. Air-pouches were washed following a 4 h IL-1 beta treatm ent, the wash collected and neutrophil number estimated using a Neubau er haemocytometer. The response to IL-IP was significantly attenuated in NK1 receptor +/- (40% reduction) and -/- mice (62% reduction) compa red to wild type controls (+/+), whilst the response to cytokine-induc ed neutrophil chemoattractant (CINC, 0.3 mu g) was unaffected. The res ponse to substance P (7.5 nmol) was attenuated by approximately 50% in both NK1 receptor +/- and -/- mice compared to wild type controls. In conclusion NK1 receptors play a significant role in the cellular resp onse to IL-1 beta in a model of inflammation.