Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-10.
Herpes simplex virus type 1 (HSV-1) infection of the murine cornea results in a tissue-destructive inflammatory response. In this study we show that virus infection induces the synthesis of macrophage inflammatory protein-2 (MIP-2), MIP-1alpha, and monocyte chemoattractant protein-1 (MCP-1). However, only the production of MIP-2 and MIP-1alpha coincided with the influx of leukocytes into the cornea. IL-10 treatment markedly suppressed chemokine message and protein synthesis in vivo. Local administration of IL-10 also dramatically reduced the number of T cells and neutrophils migrating into the cornea and suppressed the severity of corneal disease. The inflammatory response could also be suppressed by the passive transfer of neutralizing antibody to MIP-1alpha but not MCP-1. We conclude that local IL-10 administration can suppress chemokine synthesis, thereby ameliorating corneal disease. Furthermore, our results indicate that MIP-1alpha plays a major role in herpes stromal keratitis development, whereas MCP-1 does not.
Tumpey
T M
TM
Department of Microbiology and Immunology, University of South Alabama, Mobile 36688-0002, USA.
Cheng
H
H
Yan
X T
XT
Oakes
J E
JE
Lausch
R N
RN
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000502:physiology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007116:Immunization, Passive; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology*; D016849:Keratitis, Herpetic / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000502:physiology; D016133:Polymerase Chain Reaction; D013997:Time Factors
D000906:Antibodies; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016753:Interleukin-10