Vasoactive intestinal peptide (VIP) exacerbates endotoxin-induced uveitis (EIU) in mice

Curr Eye Res. 2000 Dec;21(6):913-7. doi: 10.1076/ceyr.21.6.913.6986.

Abstract

Purpose: We have previously shown that inhibition of the proinflammatory cytokine tumor necrosis factor- (TNF)-alpha exacerbates the inflammatory process of EIU. To further examine this paradoxic phenomenon, we investigated here the effect on EIU of VIP, a neuropeptide that inbibits TNF-alpha production.

Methods: VIP was injected concurrently with endotoxin at doses that induce EIU or lethality in mice. Severity of EIU was measured by counting infiltrating cells in eye sections, at 1 or 5 days post endotoxin injection. Survival of mice was monitored periodically, while serum levels of TNF-alpha, interleukin-(IL)-1beta and IL-10 were determined by caputure ELISA.

Results: Treatment with VIP exacerbated EIU but provided partial protection from the lethal endotoxin effect. VIP treatment also reduced serum levels of TNF-alpha and IL-1beta, but increased levels of IL-10.

Conclusion: This study further established the paradoxical observation that EIU is exacerbated by lowering the levels of circulating pro-inflammatory cytokines, in particular TNF-alpha.

MeSH terms

  • Animals
  • Anterior Eye Segment / pathology
  • Endotoxemia / prevention & control
  • Endotoxins / adverse effects*
  • Enzyme-Linked Immunosorbent Assay
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / blood
  • Interleukin-10 / blood
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Staphylococcal Infections / prevention & control
  • Staphylococcus*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Uveitis, Anterior / blood
  • Uveitis, Anterior / chemically induced*
  • Uveitis, Anterior / pathology
  • Vasoactive Intestinal Peptide / pharmacology*

Substances

  • Endotoxins
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Vasoactive Intestinal Peptide