Selective IL-10 inhibition of HLA-DR expression in IFN-gamma-stimulated human retinal pigment epithelial cells

Curr Eye Res. 1997 Jun;16(6):547-55. doi: 10.1076/ceyr.16.6.547.5071.


Purpose: Human RPE cells express HLA-DR antigens, bind leukocytes via ICAM-1, and secrete IL-8 and MCP-1, which attract and activate leukocytes. Since little is known concerning endogenous cytokines that may alter ocular immunologic and inflammatory mechanisms, we investigated whether IL-10, an immunosuppressive cytokine, modulates these HRPE features.

Methods: IL-10 effects on HLA-DR and ICAM-1 were examined by HRPE exposures to: (1) IFN-gamma (10-1000 U/ml) + IL-10 (1-100 U/ml) and (2) IL-10 pre-incubation followed by IFN-gamma + IL-10. Immunohistochemistry for HLA-DR and ICAM-1 was graded by masked observers. Flow cytometric analysis quantitated HRPE HLA-DR and ICAM-1. Effects of IL-10 on IL-1 beta (0.2 or 2 ng/ml)-, or TNF-alpha (0.2 or 2 ng/ml)-induced IL-8 and MCP-1 secretion and gene expression were assessed using enzyme-linked immunosorbent assay (ELISA) and Northern blot analysis.

Results: HLA-DR expression, detected by immunohistochemistry and flow cytometric analysis, showed dose-dependent increases to IFN-gamma. IL-10 pre-/co-incubation, but not co-incubation alone, markedly reduced HLA-DR expression, but did not modulate constitutive or IFN-gamma-induced ICAM-1. IL-10 alone did not induce MCP-1 or IL-8 secretion or steady-state mRNA expression, nor modulate IL-1 beta-, TNF-alpha- or IFN-gamma-induced IL-8 or MCP-1.

Conclusions: This study suggests that HRPE HLA-DR antigens are selectively inhibited by IL-10, but the timing of IL-10 exposure may be crucial.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Culture Techniques
  • HLA-DR Antigens / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon-gamma / pharmacology*
  • Interleukin-10 / pharmacology*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / metabolism*


  • Chemokine CCL2
  • HLA-DR Antigens
  • Interleukin-8
  • Intercellular Adhesion Molecule-1
  • Interleukin-10
  • Interferon-gamma