Synergistic uveitic effects of tumor necrosis factor-alpha and interleukin-1 beta.
Tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with multiple, overlapping biologic activities, have been shown to interact synergistically in nonocular tissues. To test the hypothesis that coinjection of TNF and IL-1 interact synergistically in the eye, low, marginally inflammatory doses of human recombinant TNF-alpha (4000 U), IL-1 beta (40 U), and TNF-alpha+IL-1 beta (TNF-alpha/IL-1 beta) were injected into the vitreal chamber of the rabbit eye, and inflammation was assessed at 6, 24, 48, and 168 hr post-cytokine injection. TNF-alpha/IL-1 beta induced an anterior uveitis that was barely detectable at 6 hr, increased at 24 hr, peaked at 48 hr, and largely resolved by 168 hr. Synergy was observed for infiltration of inflammatory leukocytes into aqueous humor at 24 and 48 hr and for protein and prostaglandin E levels in aqueous humor at 48 hr. Based upon protein levels in vitreous humor, TNF-alpha/IL-1 beta also induced a posterior uveitis. This posterior uveitis was not apparent until 48 hr and then increased significantly at 168 hr. At 48 and 168 hr, the effects of TNF-alpha/IL-1 beta on protein levels in vitreous humor were consistent with a synergistic interaction. Results of separate experiments using higher dose combinations of TNF-alpha/IL-1 beta and a longer time course suggested that the effects of TNF-alpha/IL-1 beta on the blood vitreous barrier persisted beyond 168 hr. The results of this study support the hypothesis that TNF-alpha and IL-1 beta interact synergistically when injected into the rabbit eye.(ABSTRACT TRUNCATED AT 250 WORDS)
Fleisher
L N
LN
Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University, College of Veterinary Medicine, Raleigh 27606.
Ferrell
J B
JB
McGahan
M C
MC
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002924:Ciliary Body / Q000201:enzymology; D004357:Drug Synergism; D005136:Eye Proteins / Q000378:metabolism; D007267:Injections; D007375:Interleukin-1 / Q000633:toxicity*; D007498:Iris / Q000201:enzymology; D007958:Leukocyte Count; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D014606:Uveitis, Anterior / Q000139:chemically induced* / Q000378:metabolism; D015866:Uveitis, Posterior / Q000139:chemically induced* / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
D005136:Eye Proteins; D007375:Interleukin-1; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase