Interleukin-10 inhibition of HLA-DR expression in human herpes stromal keratitis.

Abstract

Human herpes stromal keratitis (HSK) is an important cause of visual loss and morbidity. The presentation of corneal and/or viral antigens is thought to activate T lymphocytes, resulting in aberrant cell-mediated immune responses that are central to the pathogenesis of HSK. Aberrant cellular expression of HLA-DR and intercellular adhesion molecule-1 (ICAM-1), both of which are necessary for optimal antigen-induced T-lymphocyte responses, is present in lesions of HSK, but little is known concerning endogenous cytokines that may inhibit HLA-DR or ICAM-I expression in human disease. In this study, the authors investigated the effects of interleukin-10 (IL-10) on HLA-DR and ICAM-1 expression in human HSK. Penetrating keratoplasty specimens removed from 5 patients with HSK were divided to provide adjacent sections that were incubated with control medium or the same medium containing IL-10 (100 U/ml) for 48 hours. Immunoperoxidase staining was performed on each control and IL-10-treated corneal specimen to determine HLA-DR and ICAM-1 antigen expression. Interleukin-10 treatment resulted in profound reduction in immunoreactive HLA-DR, but not ICAM-1, in corneal cells and infiltrating leukocytes of all five HSK specimens. This study suggests that HLA-DR antigens may be selectively inhibited by cytokines released during inflammation in HSK. These results are the first to demonstrate cytokine suppression of HLA-DR in a human disease. Pharmacologic doses of IL-10 may inhibit HLA-DR-dependent immune responses that underlie a variety of destructive ocular inflammatory diseases.