IL-12 inhibits endotoxin-induced inflammation in the eye.
Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. The goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. The number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. In contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. The infiltrating inflammatory cells were reduced in the eyes of animals receiving intraocular IL-12 when compared to controls. Cytokine analysis of the aqueous humor obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and suggest that IL-12 can have an immunoregulatory function in some forms of inflammatory disease.
Whitcup
S M
SM
National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA.
Rizzo
L V
LV
Lai
J C
JC
Hayashi
S
S
Gazzinelli
R
R
Chan
C C
CC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001082:Aqueous Humor / Q000737:chemistry; D001427:Bacterial Toxins / Q000633:toxicity*; D016207:Cytokines / Q000032:analysis; D004731:Endotoxins / Q000633:toxicity*; D005123:Eye / Q000187:drug effects; D005260:Female; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000276:immunology; D014605:Uveitis / Q000209:etiology* / Q000473:pathology* / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D016207:Cytokines; D004731:Endotoxins; D011994:Recombinant Proteins; C027952:salmonella toxin; D018664:Interleukin-12