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


CONCLUSIONS
This study further established the paradoxical observation that EIU is exacerbated by lowering the levels of circulating pro-inflammatory cytokines, in particular TNF-alpha.
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, Maryland, United States of America. zhangm@intra.nei.nih.gov
M
M
Zhang
L
L
Hung
I
I
Gery
D000818:Animals; D000869:Anterior Eye Segment / Q000473:pathology; D019446:Endotoxemia / Q000517:prevention & control; D004731:Endotoxins / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013203:Staphylococcal Infections / Q000517:prevention & control; D013210:Staphylococcus; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014606:Uveitis, Anterior / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D004731:Endotoxins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014660:Vasoactive Intestinal Peptide