Impaired IL-1β-induced neutrophil accumulation in tachykinin NK1 receptor knockout mice

Abstract

Tachykinin NK1 receptors play an important role in the development of neurogenic inflammatory responses. We have used the murine air-pouch model to investigate whether the neurogenic component of the cellular inflammatory response to interleukin-1β (IL-1β, 10 ng into the air-pouch) is altered in NK1 receptor knockout mice compared to wild type controls. Air-pouches were washed following a 4 h IL-1β treatment, the wash collected and neutrophil number estimated using a Neubauer haemocytometer. The response to IL-1β was significantly attenuated in NK1 receptor +/- (40% reduction) and -/- mice (62% reduction) compared to wild type controls (+/+), whilst the response to cytokine-induced neutrophil chemoattractant (CINC, 0.3 μg) was unaffected. The response 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 response to IL-1β in a model of inflammation.