Time course and cellular localization of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system.
Experimental autoimmune encephalomyelitis of the Lewis rat is a T-cell-mediated autoimmune disease of the central nervous system characterized by a self-limiting monophasic course. In this study, we analyzed the expression of the anti-inflammatory cytokine interleukin (IL)-10 at the mRNA and protein level in experimental autoimmune encephalomyelitis actively induced with the encephalitogenic 68-86 peptide of guinea pig myelin basic protein. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-10 mRNA expression peaked during the acute phase of the disease at days 11 and 13. IL-10 mRNA was synchronously induced with mRNA for the proinflammatory cytokine interferon-gamma. Immunocytochemistry with a monoclonal antibody against rat IL-10 showed that the peak of IL-10 mRNA was accompanied by an abundant expression of IL-10 protein during the acute stage of the disease. Both in situ hybridization and double labeling immunocytochemistry in combination with confocal microscopy identified T cells, macrophages/microglia, and astrocytes as major cellular sources of IL-10 in vivo. The early peak of IL-10 production was unexpected in light of its well-documented anti-inflammatory properties. Additional studies are required to determine whether endogenous IL-10 contributes to rapid clinical remission typical for Lewis rat experimental autoimmune encephalomyelitis or if it plays other, yet undefined, roles in central nervous system autoimmunity.
Jander
S
S
Department of Neurology, Center for Biological and Medical Research, Heinrich-Heine-University, Düsseldorf, Germany. jander@neurologie.uni-duesseldorf.de
Pohl
J
J
D'Urso
D
D
Gillen
C
C
Stoll
G
G
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D009418:S100 Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D012333:RNA, Messenger; D009418:S100 Proteins; D016753:Interleukin-10; D007371:Interferon-gamma