SYSTEMIC CYTOKINE IMMUNOTHERAPY FOR EXPERIMENTAL CYTOMEGALOVIRUS RETINITIS IN MICE WITH RETROVIRUS-INDUCED IMMUNODEFICIENCY

Purpose. To evaluate and compare the in vivo administration of interle ukin-2 (IL-2) or interleukin-12 (IL-12) in the immunotherapy of necrot izing retinitis caused by murine cytomegalovirus (MCMV) in mice with a retrovirus-induced immunodeficiency syndrome (MAIDS). Methods. Adult C57BL/6 mice with MAIDS of 8 weeks' duration were treated with either a single intramuscular injection of polyethylene glycol-modified human recombinant IL-2 (PEG-IL-2) or multiple intramuscular injections of m urine recombinant IL-12; untreated mice with MAIDS received phosphate- buffered saline. Two days later, the left eyes of all mice were inocul ated with MCMV by subretinal injection and evaluated at day 6 for intr aocular MCMV titers or at day 10 for frequency of necrotizing MCMV ret initis. Results. Infectious MCMV was significantly reduced in whole ey es of PEG-IL-2-treated mice with MAIDS (2.8 log(10)), but not in whole eyes of IL-12-treated animals (4.4 log(10)) when compared with whole eyes of untreated animals with MAIDS (4.5 log(10)). Similarly, whereas eyes from similar to 80% of IL-12-treated and untreated mice with MAI DS showed histopathologic features consistent with classic necrotizing MCMV retinitis (full-thickness retinal necrosis associated with virus inclusions and cytomegalocytes), none (0%) of PEG-IL-2-treated animal s with MAIDS showed classic MCMV retinitis. Instead, eyes from these a nimals showed either retinal folding or outer retinal atrophy, a patte rn of histopathology similar to that observed in eyes from immunologic ally normal C57BL/6 mice inoculated subretinally with MCMV. Conclusion s. These results provide proof-of-principle for the hypothesis that sy stemic cytokine immunotherapy will reduce the frequency of CMV retinit is in a setting of retrovirus-induced immunosuppression. Because of th e striking differential effects of IL-2 and IL-12 on MCMV-retinitis in mice with MAIDS, the authors conclude that cytokine immunotherapy for cytomegalovirus-induced retinitis is cytokine-specific, even for such cytokines as IL-2 and IL-12 that have T cell regulation in common.