Differential induction of interleukin-12, interleukin-18, and interleukin-1beta converting enzyme mRNA in experimental autoimmune encephalomyelitis of the Lewis rat.
Experimental autoimmune encephalomyelitis (EAE) is a model of autoimmune central nervous system (CNS) disease that is mediated by autoreactive Th1 cells secreting the proinflammatory cytokine interferon (IFN)-gamma. Interleukin (IL)-12 in its heterodimeric p35/p40 isoform and the recently described cytokine IL-18 potently induce T cell production of IFN-gamma. Interleukin-1beta converting enzyme (ICE) is required to convert IL-18 precursor protein into its biologically active mature form. In this study, we used semiquantitative reverse transciptase-polymerase chain reaction to determine steady state levels of IL-12, IL-18, and ICE mRNA in the spinal cord of Lewis rats at different stages of EAE. In control rats, we found significant IL-18, ICE, and IL-12p35, but not IL-12p40 mRNA expression. IL-18 mRNA increased during the acute stage of EAE together with a marked induction of ICE mRNA. IL-12p35 mRNA levels did not change significantly throughout the course of EAE. Surprisingly, the peak expression of IL-12p40 mRNA was delayed by several days relative to the peak of T cell infiltration and IFN-gamma mRNA synthesis. Our data implicate the IL-18/ICE pathway in the amplification of Th1-mediated immune responses in the CNS but suggest a different, so far undefined role of endogenous IL-12 in the late effector phase of EAE.
Jander
S
S
Department of Neurology and Center for Biological and Medical Research, Heinrich-Heine-University, Düsseldorf, Germany. jander@neurologie.uni-duesseldorf.de
Stoll
G
G
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D020170:Caspase 1 / Q000235:genetics* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006168:Guinea Pigs; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017252:CD3 Complex; D020382:Interleukin-18; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D018664:Interleukin-12; D020170:Caspase 1