Systemic cytokine immunotherapy for experimental cytomegalovirus retinitis in mice with retrovirus-induced immunodeficiency.

Abstract

PURPOSE:

To evaluate and compare the in vivo administration of interleukin-2 (IL-2) or interleukin-12 (IL-12) in the immunotherapy of necrotizing 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 murine recombinant IL-12; untreated mice with MAIDS received phosphate-buffered saline. Two days later, the left eyes of all mice were inoculated with MCMV by subretinal injection and evaluated at day 6 for intraocular MCMV titers or at day 10 for frequency of necrotizing MCMV retinitis.

RESULTS:

Infectious MCMV was significantly reduced in whole eyes of PEG-IL-2-treated mice with MAIDS (2.8 log10), but not in whole eyes of IL-12-treated animals (4.4 log10) when compared with whole eyes of untreated animals with MAIDS (4.5 log10). Similarly, whereas eyes from approximately 80% of IL-12-treated and untreated mice with MAIDS 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 animals with MAIDS showed classic MCMV retinitis. Instead, eyes from these animals showed either retinal folding or outer retinal atrophy, a pattern of histopathology similar to that observed in eyes from immunologically normal C57BL/6 mice inoculated subretinally with MCMV.

CONCLUSIONS:

These results provide proof-of-principle for the hypothesis that systemic cytokine immunotherapy will reduce the frequency of CMV retinitis in a setting of retrovirus-induced immunosuppression. Because of the 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.

• Authors: R D Dix, M Giedlin, S W Cousins
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 38 Issue 7 Pg. 1411-7 (Jun 1997) ISSN: 0146-0404 [Print] United States
• PMID: 9191604 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-2
• Interleukins
• Recombinant Proteins
• Interleukin-12
• Polyethylene Glycols

Topics

• Animals
• Disease Models, Animal
• Eye Infections, Viral (etiology, pathology, therapy)
• Female
• Herpesviridae Infections (etiology, pathology, therapy)
• Immunotherapy
• Interleukin-12 (therapeutic use)
• Interleukin-2 (therapeutic use)
• Interleukins (therapeutic use)
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Murine Acquired Immunodeficiency Syndrome (etiology, pathology, therapy)
• Muromegalovirus (isolation & purification)
• Polyethylene Glycols
• Recombinant Proteins (therapeutic use)
• Retina (drug effects, pathology, virology)
• Retinitis (pathology, therapy, virology)