Interleukin-6 does not mediate endotoxin-induced uveitis in mice: studies in gene deletion animals.
OBJECTIVE
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.
Rosenbaum
J T
JT
Casey Eye Institute, Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201-4197, USA.
Kievit
P
P
Han
Y B
YB
Park
J M
JM
Planck
S R
SR
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004731:Endotoxins; D004926:Escherichia coli; D017353:Gene Deletion; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains / Q000235:genetics; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
D016207:Cytokines; D017931:DNA Primers; D004731:Endotoxins; D015850:Interleukin-6