IL-12 EXACERBATES HELMINTH-MEDIATED CORNEAL PATHOLOGY BY AUGMENTING INFLAMMATORY CELL RECRUITMENT AND CHEMOKINE EXPRESSION

Corneal inflammation (keratitis) is a major cause of visual impairment in Onchocerca volvulus infection. Previous studies showed that onchoc ercal keratitis can be induced in mice following s.c. immunization and intracorneal injection with soluble O. volvulus Ags (OvAg), and that the inflammatory response is dependent on T cells and IL-4. Since reco mbinant IL-12 impairs IL-4-dependent, Th2-mediated responses in other parasitic infections and in models of allergic asthma, the present stu dy was undertaken to determine the effect of IL-12 on onchocercal kera titis. Mice were injected i.p. with IL-12 or saline at the time of ini tial sensitization to OvAg. Surprisingly, IL-12 treatment caused signi ficant exacerbation of corneal pathology, which was associated with in creased eosinophil and mononuclear cell infiltration into the corneal stroma. Consistent with the well-documented effect of IL-12 on Th1 cel l development, corneas of IL-12-treated animals had elevated expressio n of the Th1 cytokine IFN-gamma and diminished expression of the Th2 c ytokines IL-4, IL-5, IL-10, and IL-13. However, corneas from these ani mals also had marked elevation of alpha- and beta-chemokines known to be active on eosinophils and mononuclear cells, including IFN-gamma-in ducible protein (IP)-10, macrophage inflammatory protein-1 alpha, macr ophage inflammatory protein-1 beta, JE/monocyte chemotactic protein-1, RANTES (regulated upon activation, normal T expressed and secreted), and eotaxin. Together, these data indicate that IL-12 exacerbates OvAg -mediated corneal pathology by enhancing chemokine expression and recr uitment of inflammatory cells.