Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea.
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-alpha-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-1alpha, 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.
Yan
X T
XT
Department of Miicrobiology and Immunology, School of Medicine, University of South Alabama, Mobile 36688, USA.
Zhuang
M
M
Oakes
J E
JE
Lausch
R N
RN
D000818:Animals; D019898:Autocrine Communication / Q000276:immunology*; D003315:Cornea / Q000276:immunology* / Q000821:virology*; D003316:Corneal Diseases / Q000276:immunology / Q000821:virology*; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
D016753:Interleukin-10