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S. A. McClellan, R. P. Barrett, Y. Zhang, L. D. Hazlett; Substance P Exacerbates P. Aeruginosa Keratitis in Resistant BALB/c Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2657.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that blocking Substance P (SP) binding to its major receptor, the neurokinin 1 receptor (NK1-R) by Spantide I injection, prevents P. aeruginosa induced corneal perforation in susceptible C57BL/6 mice. The purpose of this study was to determine the effect of exogenously injected SP in the resistance response (cornea heals) of BALB/c mice.
Mice were injected intraperitoneally with SP (15 µM) or PBS the day before infection. Disease was graded by clinical score, slit lamp, PMN quantitation (MPO assay), bacterial plate count, real time RT-PCR and ELISA assay.
BALB/c mice injected with SP exhibited worsened disease on days 1-7 postinfection (p.i.) when compared to PBS controls. SP injection resulted in elevated PMN and viable bacterial counts in the cornea at both 3 and 5 days p.i. Type I cytokines (e.g., IFN-γ), as well as TNF-α, MIP-2, IL-18, IL-6, and IL-1ß (mRNA and protein) also were significantly elevated, while type 2 cytokines TGF-ß and IL-10 (mRNA and protein) were significantly reduced.
These data suggest that the neuropeptide, SP, found at higher levels in the cornea of C57BL/6 mice, is a potent neuro-immunoregulator that can promote susceptibility in the resistant BALB/c mouse by overcoming the anti-inflammatory effects of the type 2 cytokine, IL-10.
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