INTERLEUKIN-10 INHIBITION OF HLA-DR EXPRESSION IN HUMAN HERPES STROMAL KERATITIS

Purpose: Human herpes stromal keratitis (HSK) is an important cause of visual loss and morbidity. The presentation of corneal and/or viral a ntigens is thought to activate T lymphocytes, resulting in aberrant ce ll-mediated immune responses that are central to the pathogenesis of H SK. Aberrant cellular expression of HLA-DR and intercellular adhesion molecule-1 (ICAM-1), both of which are necessary for optimal antigen-i nduced T-lymphocyte responses, is present in lesions of HSK, but littl e is known concerning endogenous cytokines that may inhibit HLA-DR or ICAM-1 expression in human disease. In this study, the authors investi gated the effects of interleukin-10 (IL-10) on HLA-DR and ICAM-1 expre ssion in human HSK. Methods: Penetrating keratoplasty specimens remove d from 5 patients with HSK were divided to provide adjacent sections t hat were incubated with control medium or the same medium containing 1 L-10 (100 U/ml) for 48 hours. Immunoperoxidase staining was performed on each control and IL-10-treated corneal specimen to determine HLADR and ICAM-1 antigen expression. Results: Interleukin-10 treatment resul ted in profound reduction in immunoreactive HLA-DR, but not ICAM-1, in corneal cells and infiltrating leukocytes of all five HSK specimens. Conclusions: This study suggests that HLA-DR antigens may be selective ly inhibited by cytokines released during inflammation in HSK. These r esults are the first to demonstrate cytokine suppression of HLA-DR in a human disease. Pharmacologic doses of IL-10 may inhibit HLA-DR-depen dent immune responses that underlie a variety of destructive ocular in flammatory diseases.