Macrophage-inactivating IL-13 suppresses experimental autoimmune encephalomyelitis in rats.
Experimental autoimmune encephalomyelitis (EAE) is initiated by myelin basic protein (MBP)-specific CD4+ T cells of the Th1 phenotype that subsequently trigger the invasion of monocytes/macrophages into the brain. In this study, we evaluated the potential of human recombinant (hr) IL-13 to exert a protective effect on the development of EAE in Lewis rats. hrIL-13 is found to be a potent in vitro modulator of various rat macrophage functions, including an inhibition of the production of the proinflammatory cytokines IL-1 beta and TNF, and a simultaneous enhancement of MHC class II and CD4 receptor expression. Furthermore, hrIL-13 displayed a slight, but highly reproducible, inhibitory effect on the in vitro proliferative responses of encephalitogenic MBP-specific T cells stimulated in the presence of thymic APCs. Upon in vivo application of hrIL-13-secreting vector cells into MBP-immunized animals, the cytokine was capable of markedly suppressing the development of EAE, as assessed by a reduction of the mean duration, severity, and incidence of disease. This suppression of disease coincided with an only minimal reduction of MBP-directed T cell autoreactivity and no alteration in MBP-specific autoantibody production. We infer from these results that a strictly Th1-initiated immune disease can be attenuated efficiently by the administration of a cytokine that primarily targets cells of the macrophage/monocyte lineage and seems to exert no undesirable general suppression on either T cell or B cell immunoreactivity in vivo.
Cash
E
E
INSERM U 283, Cochin Hospital, Paris, France.
Minty
A
A
Ferrara
P
P
Caput
D
D
Fradelizi
D
D
Rott
O
O
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D017628:Microglia / Q000187:drug effects; D004676:Myelin Basic Protein / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D018793:Interleukin-13; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide