The role of IL-12 in the induction of late-phase cellular infiltration in a murine model of allergic conjunctivitis

Background: The applied murine model of allergic conjunctivitis mimics human disease, and an immediate hypersensitivity reaction (LHR) and a late-phase cellular reaction typically develop in sensitized mice after topical challenge with the allergen. Objective: We investigated the role of IL-4, IFN-gamma, and IL-12 in the early and late phases of ocular allergy with use of cytokine knockout (KO) mice and neutralizing antibodies. Methods: Ragweed-sensitized wild-type or IL-4KO, IL-12KO, IFN-gamma KO, anti-IL-12 mAb-treated, recombinant murine IL-12-treated, and anti-IFN-gamma mAb-treated mice were challenged with the allergen 10 days after the immunization, IHR, cellular infiltration, lymphoproliferative response, and cytokine production from draining lymph nodes were recorded and compared among groups. Results: We show that IL-12KO mice and anti-IL-12 antibody-treated wild-type animals failed to have a cellular infiltration into the conjunctiva. Treatment with recombinant murine IL-12 also reduced the number of infiltrating PMNs but increased the percentage of mononuclear cells in the conjunctiva compared with controls, IFN-gamma KO mice had a significantly stronger MR and prolonged infiltration into the conjunctiva after challenge with ragweed than controls. Conclusion: Our data suggest that the presence of IL-12, although better known as a T(H)1-inducing cytokine, is important for the development and the regulation of the late-phase pathologic features in ocular allergy. Furthermore, IFN-gamma is a limiting factor in the late phase of allergy and thus may be important in preventing chronic allergic disease.