IL-12 INHIBITS ENDOTOXIN-INDUCED INFLAMMATION IN THE EYE

Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interf eron (IFN)-gamma production and an increased generation of Th 1 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 endo toxin-induced ocular inflammation. The number of inflammatory cells in filtrating 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 infi ltrating 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 intraocu lar inflammation. The inflammatory cells were reduced in the eves of a nimals receiving intraocular IL-obtained from eyes with EIU showed inc reased levels of IFN-gamma and decreased levels of IL-6 in eyes receiv ing intraocular IL-12. These data show that IL-12 has an inhibitory ef fect on endotoxin-induced inflammation in the eye and su that IL-12 ca n have an immunoregulatory function in some forms of inflammatory dise ase.