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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Boorstein
S M
SM
Department of Ophthalmology, University of Michigan, Ann Arbor 48105.
Elner
S G
SG
Meyer
R F
RF
Sugar
A
A
Strieter
R M
RM
Kunkel
S L
SL
Elner
V M
VM
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003319:Corneal Stroma / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10 / Q000494:pharmacology*; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged
D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10