Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea

• Published in: Journal of leukocyte biology Vol. 69; no. 1; pp. 149 - 157
• Main Authors: Yan, Xiao‐Tian, Zhuang, Minsheng, Oakes, John E., Lausch, Robert N.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.01.2001
• Subjects: Animals; Autocrine Communication - immunology; chemokines; Cornea - immunology; Cornea - virology; Corneal Diseases - immunology; Corneal Diseases - virology; corneal epithelial cells; corneal fibroblasts; cytokines; Female; Herpes Simplex - immunology; herpes simplex virus 1; Herpesvirus 1, Human - immunology; IL‐10 knockout mice; IL‐10 receptor; Inflammation - immunology; Interleukin-10 - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; MIP-1^a protein; MIP-2 protein; tumor necrosis factor-^a
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.69.1.149

We investigated whether IL‐10 produced endogenously would influence the development of HSV‐1‐induced acute corneal disease. Murine corneal epithelial cells and fibroblasts cultured in vitro expressed IL‐10 mRNA and protein constitutively and also IL‐10 receptors. Inclusion of IL‐10 neutralizing antibody in the culture medium significantly (p<0.05) enhanced TNF‐α‐induced IL‐6 and MIP‐2 production by both corneal cell types. Endogenous IL‐10 synthesis, which also occurred in vivo, was not modulated by Herpes virus infection or by depletion of neutrophils or natural killer cells. Antibody to IL‐10 given locally at the time of HSV‐1 intracorneal infection was associated with significantly (p<0.05) enhanced production of IL‐6, MIP‐2, and MIP‐1α, increased neutrophil infiltration, and more extensive corneal disease. Similarly, mice with a disrupted IL‐10 gene developed more severe corneal disease than wild‐type controls. Collectively, these observations suggest that locally produced IL‐10 can act in an autocrine/paracrine fashion to down‐regulate the production of proinflammatory mediators and thus limit corneal inflammation.