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)