Increased weight loss with reduced viral replication in interleukin-10 knock-out mice infected with murine cytomegalovirus.
The anti-inflammatory cytokine interleukin (IL)-10 plays an important role in the regulation of host-immune responses. Here we studied the role IL-10 plays in host responses to cytomegalovirus (CMV) infection. We demonstrate that manifestations of murine CMV (MCMV) disease are more severe in IL-10 knock-out mice, despite significantly reduced levels of viral replication. Cytokine analysis of serum revealed increased levels of interferon (IFN)-gamma, monocyte chemotactic protein 1 (MCP-1) and IL-6, all of which are potent stimulators of inflammatory responses. Depletion of IFN-gamma by monoclonal antibodies in IL-10 knock-out mice failed to improve the physical condition of the mice, while increasing viral replication. In contrast, serum levels of IL-6 in the knock-out animals were unaffected by IFN-gamma depletion and remained significantly elevated early in the course of infection. These data suggest that increased weight loss observed in IL-10 knock-out mice may be attributed to the uncontrolled production of proinflammatory cytokines, including IL-6.
Oakley
O R
OR
Department of Clinical Sciences, University of Kentucky, Lexington, KY 40536-0084, USA. oroakl1@email.uky.edu
Garvy
B A
BA
Humphreys
S
S
Qureshi
M H
MH
Pomeroy
C
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018932:Chemokine CCL2 / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation; D014779:Virus Replication; D015431:Weight Loss
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma