Abstract
Purpose: :
In Pseudomonas aeruginosa ocular infection, dominant T–helper cell 1 (Th1)–responsive mouse strains are susceptible (cornea perforates), while Th2–responsive mouse strains are resistant (cornea heals). Neuropeptides are endogenous neuroendocrine factors that have recently been correlated with neuroimmune interaction and function, but little is known of their role in mediating or regulating ocular infectious disease. Previous studies have shown an increased level of expression for vasoactive intestinal peptide (VIP), a neuropeptide associated with potent anti–inflammatory activities, in BALB/c (Th2–responder) vs. C57BL/6 (B6) (Th1–responder) mice. Therefore, the purpose of this study was to examine the role of VIP in modulating the host immune response to P. aeruginosa–induced keratitis.
Methods: :
B6 mice were injected intraperitoneally with recombinant (r) VIP daily from –1 through 7 days p.i. Control mice were similarly injected with PBS. Clinical scores, slit–lamp, viable bacterial plate counts, myeloperoxidase (MPO) for PMN quantitation, multiprobe ribonuclease protection assays (RPA) and real–time RT–PCR were used to assess the effects of rVIP treatment in modulating disease pathogenesis.
Results: :
Injection of B6 mice with rVIP prevented corneal perforation, normally seen in the susceptible animal by 5–7 days p.i. Real–time RT–PCR analysis of rVIP versus control corneas showed significantly decreased levels for IFN–γ, IL–1ß, MIP–2 and TNF–α mRNA at 7 days p.i. Bacterial load remained comparable for rVIP versus control animals, while PMN infiltration appeared more controlled upon rVIP treatment.
Conclusions: :
These data provide evidence that VIP is a regulatory molecule of ocular inflammation. rVIP treatment counterbalanced the production of pro–inflammatory cytokines, IFN–γ and IL–1ß, and regulated PMN infiltration sufficiently to ameliorate the host–induced component of bacterial–induced inflammatory disease.
Keywords: cornea: basic science • bacterial disease • immunomodulation/immunoregulation