Interleukin-10 treatment can suppress stromal keratitis induced by herpes simplex virus type 1.
Herpes simplex virus type 1 (HSV-1) infection of the murine cornea induces an intense inflammatory response that can lead to permanent blindness. We tested whether IL-10, a cytokine that has anti-inflammatory properties, could suppress the development of stromal disease. Murine rIL-10 was inoculated intracorneally 4 before and again on days +2 and +5 relative to the time of topical HSV-1 corneal infection. Additionally, the mice received IL-10 i.p. at the time of virus administration and again 3 days post-infection. Four weeks post-infection, the incidence of blinding disease was 95% in the saline-treated controls but only 36% in the IL-10-treated animals. Histologic studies showed extensive cellular infiltrates in control corneas but not in those of the IL-10-treated eyes. Examination of the proinflammatory cytokine levels in the cornea 10 days after infection revealed that the presence of IL-2 was 10-fold lower and IL-6 some 50-fold lower than that found in the controls. IL-1 alpha levels were not reduced. The IL-10 treatment protocol employed did not suppress the systemic cellular or humoral immune responses to viral Ag, nor was the rate of HSV-1 clearance from the eye different from that seen in the controls. In vitro studies revealed that spontaneous production of IL-6 by excised normal corneas was inhibited by > 95% with low dose IL-10. IL-1 alpha synthesis was not inhibited. Collectively, these results indicate that IL-10 treatment can 1) suppress the production of certain cytokines produced by corneal cells, and 2) minimize ocular inflammation without compromising clearance of the infecting virus from the eye.
Tumpey
T M
TM
Department of Microbiology and Immunology, University of South Alabama, College of Medicine, Mobile 36688.
Elner
V M
VM
Chen
S H
SH
Oakes
J E
JE
Lausch
R N
RN
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation; D003315:Cornea / Q000378:metabolism; D005260:Female; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D014779:Virus Replication / Q000187:drug effects
D000914:Antibodies, Viral; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016753:Interleukin-10