Systemic interferon-gamma suppresses the development of endotoxin-induced uveitis in mice.
OBJECTIVE
It has been shown that interferon (IFN)-gamma is involved in the development of endotoxin-induced uveitis (EIU), but its exact role is unclear. We aimed to elucidate the role that endogenous systemic IFN-gamma plays in EIU pathogenesis.


METHODS
EIU was induced in wild-type (WT) or IFN-gamma knockout (GKO) mice on the C57BL/6 background by injecting Salmonella typhimurium endotoxin into a hind footpad. Twenty-four hours later, the eyes were harvested for histological analysis, and the serum was collected for cytokine ELISAs. WT and GKO mice were also intraperitoneally injected with 1 microg of recombinant murine IFN-gamma (rmIFN-gamma) just after and 6 h after EIU induction, and their eyes and sera were evaluated 24 h after EIU induction, as above.


RESULTS
The GKO mice had significantly more severe EIU as determined by the number of ocular infiltrating cells and lower serum IL-6 levels after EIU induction compared to WT mice. The injection of rmIFN-gamma suppressed the severity of EIU and increased the serum IL-6 levels in both the WT and GKO mice.


CONCLUSIONS
Endogenous IFN-gamma suppresses EIU pathogenesis. In addition, the systemic administration of IFN-gamma suppresses EIU. The suppressive mechanism involved is unclear but may relate to the production of IL-6.
Fukushima
Atsuki
A
Laboratory of Immunology, Department of Ophthalmology, Kochi Medical School, Kochi University, Nankoku City, Japan. fukusima@med.kochi-u.ac.jp
Ozaki
Akemi
A
Ishida
Waka
W
Fukata
Kazuyo
K
Ueno
Hisayuki
H
D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000502:physiology* / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D004731:Endotoxins; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma