Exogenous IL-12 suppresses experimental autoimmune encephalomyelitis (EAE) by tuning IL-10 and IL-5 levels in an IFN-gamma-dependent way.
Endogenous IL-12 is considered to be required for the generation and function of pathogenic Th1 effector cells in experimental autoimmune encephalomyelitis (EAE). We show here that IL-12 administration together with the immunization suppressed actively induced CREAE in SJL/J and in Biozzi/ABH mice and even subsequent spontaneous relapse incidence and severity in Biozzi ABH mice. IL-12 given during remission of primary disease inhibited re-induced relapses in SJL/J, but not spontaneous relapses in Biozzi mice. The protective effect of IL-12 is time- and dose-dependent. Protection is accompanied by subsequent increased production of IL-10 and IL-5 by lymph node and spleen cells and an inhibition of cell proliferation. Mice depleted of IFN-gamma by administration of neutralizing antibodies were poorly protected by exogenous IL-12, indicating that the inhibitory effect of IL-12 is partially IFN-gamma dependent.
Berghmans
Nele
N
Laboratory of Immunobiology, Rega Institute, University of Leuven Medical School, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Dillen
Chris
C
Heremans
Hubertine
H
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D013116:Spinal Cord / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015848:Interleukin-5; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma