Paradoxical effects of IL-10 in endotoxin-induced uveitis.
Uveitis, or intraocular inflammation, can be provoked in laboratory rodents by the local or systemic injection of bacterial endotoxin. Many of the inflammatory effects of endotoxin are potentially due to the induction of cytokine synthesis. IL-10 is a cytokine that potently inhibits the synthesis of many cytokines, including IL-1 and TNF-alpha. We have assessed the ability of IL-10 to inhibit endotoxin-induced uveitis in rabbits and mice. The intravitreal injection of 1 micrograms of human recombinant IL-10 was extremely effective in rabbits in reducing the inflammation produced by the intravitreal injection of 250 ng of Escherichia coli endotoxin, as judged by the reduced accumulation of cells and protein in the aqueous humor. Locally injected IL-10 was similarly effective in blocking the ocular inflammatory effects of intravitreally injected endotoxin in a mouse model. If the injection of IL-10 was delayed subsequent to the endotoxin injection, the reduced inflammatory effects in the rabbit model were diminished. In contrast to its ability to inhibit the local inflammatory effect of endotoxin in the eye, IL-10 did not reduce the inflammation induced by a local ocular injection of 400 U of human recombinant IL-alpha. Paradoxically, in a mouse model of uveitis subsequent to intraperitoneally injected endotoxin, the simultaneous injection of 1 micrograms of IL-10 and endotoxin potentiated the ocular inflammation, as judged by the number of leukocytes seen in histologic sections. This effect was dose dependent, since eye inflammation was markedly inhibited by 100 micrograms of IL-10 injected i.p. These observations are compatible with the hypothesis that locally injected IL-10 acts by reducing cytokine synthesis in these uveitis models. Intraperitoneally injected IL-10 can either inhibit or suppress endotoxin-induced eye inflammation in a dose-dependent manner.
Rosenbaum
J T
JT
Oregon Health Sciences University, Casey Eye Institute, Portland 97201, USA.
Angell
E
E
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004731:Endotoxins / Q000037:antagonists & inhibitors; D005260:Female; D007267:Injections; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011817:Rabbits; D015829:Uveitis, Suppurative / Q000209:etiology / Q000628:therapy*
D016207:Cytokines; D004731:Endotoxins; D016753:Interleukin-10