Corneal
infection with Pseudomonas aeruginosa perforates the cornea in susceptible C57BL/6 (B6), but not resistant BALB/c, mice. To determine whether
vasoactive intestinal peptide (VIP) played a role in development of the resistant response,
protein expression levels were tested by immunocytochemistry and
enzyme immunoassay in BALB/c and B6 corneas. Both mouse strains showed constitutive expression of corneal VIP
protein and nerve fiber distribution. However, disparate expression patterns were detected in the cornea after
infection. VIP
protein was elevated significantly in BALB/c over B6 mice at 5 and 7 days postinfection. Therefore, B6 mice were injected with rVIP and subsequently demonstrated decreased
corneal opacity and resistance to
corneal perforation compared with PBS controls. rVIP- vs PBS-treated B6 mice also demonstrated down-regulation of corneal
mRNA and/or
protein levels for proinflammatory
cytokines/
chemokines: IFN-gamma, IL-1beta, MIP-2, and
TNF-alpha, whereas anti-inflammatory mediators,
IL-10 and
TGF-beta1, were up-regulated. Treatment with rVIP decreased NO levels and polymorphonuclear neutrophil (PMN) number. To further define the role of VIP, peritoneal macrophages (Mphi) and PMN from BALB/c and B6 mice were stimulated with LPS and treated with rVIP. Treatment of LPS-stimulated Mphi from both mouse strains resulted in decreased IL-1beta and MIP-2
protein levels; PMN responded similarly. Both cell types also displayed a strain-dependent differential response to rVIP, whereby B6 Mphi/PMN responded only to a higher concentration of VIP compared with cells from BALB/c mice. These data provide evidence that neuroimmune regulation of the
cytokine network and host inflammatory cells functions to promote resistance against P. aeruginosa corneal
infection.