Interleukin-6 does not mediate endotoxin-induced uveitis in mice: studies in gene deletion animals

Abstract

Purpose: Interleukin-6 (IL-6) has been strongly implicated in anterior uveitis based on its presence in aqueous humor from infected eyes and its inflammatory effects when injected intravitreally into rats. We used IL-6-deficient mice to test further the hypothesis that IL-6 contributes to the development of endotoxin-induced uveitis.

Methods: Uveitis was scored by histologic analysis of C3H/HeN mice 24 hours after intravitreal injections of up to 200 ng of recombinant murine IL-6. Uveitis was similarly measured in IL-6-deficient mice and congenic controls 24 hours after intravitreal injection of 250 ng of Escherichia coli endotoxin. Reverse transcription-polymerase chain reaction was used to detect mRNAs for several cytokines at 3 hours postinjection. The IL-6 concentration in aqueous humor samples was determined with a bioassay using the murine B9 plasmacytoma cell line.

Results: Direct injection of IL-6 did not induce uveitis. Mice genetically deficient in IL-6 developed endotoxin-induced uveitis that was comparable or more severe than congenic control mice. Compensatory changes in the expression of mRNA for other cytokines were not detected in irises from the IL-6-deficient mice. In IL-6-competent mice that received bilateral endotoxin injections, no correlation was found between the number of infiltrating cells in one eye and the IL-6 concentration in the aqueous humor of the contralateral eye.

Conclusions: In marked contrast to previous conclusions with rats, IL-6 was not sufficient for inducing uveitis in mice. Additionally, IL-6 was not necessary for the development of uveitis subsequent to intravitreal injection of endotoxin in mice.