Impaired IL-1beta-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 model to investigate whether the neurogenic component of the cellular inflammatory response to interleukin-1beta (IL-1beta, 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-1beta treatment, the wash collected and neutrophil number estimated using a Neubauer haemocytometer. The response to IL-1beta 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 microg) 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-1beta in a model of inflammation.
Centre for Clinical Pharmacology, The Cruciform Project, UCL, The Rayne Institute, London, UK.
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Ahluwalia
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De Felipe
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O'Brien
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Hunt
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Perretti
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D013373:Substance P / Q000494:pharmacology
D018836:Inflammation Mediators; D007375:Interleukin-1; D018040:Receptors, Neurokinin-1; D013373:Substance P