Department of Microbiology and Immunology, School of Medicine, University of South Alabama, Mobile, Alabama
Correspondence: Dr. Robert N. Lausch, Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL 36688. E-mail: rlausch{at}jaguer1.usouthal.edu
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-
-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-1,
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.
Key Words: cytokines • chemokines • IL-10 knockout mice • IL-10 receptor • corneal fibroblasts • corneal epithelial cells
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