Macrophage-inactivating IL-13 suppresses experimental autoimmune encephalomyelitis in rats

• Published in: The Journal of immunology (1950) Vol. 153; no. 9; pp. 4258 - 4267
• Main Authors: Cash, E, Minty, A, Ferrara, P, Caput, D, Fradelizi, D, Rott, O
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.11.1994
• Subjects: Animals; CD4 Antigens - biosynthesis; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Histocompatibility Antigens Class II - biosynthesis; Interleukin-1 - biosynthesis; Interleukin-13 - pharmacology; Lymphocyte Activation - immunology; Lymphocyte Subsets - drug effects; Lymphocyte Subsets - immunology; Macrophages - drug effects; Male; Microglia - drug effects; Myelin Basic Protein - immunology; Nitric Oxide - biosynthesis; Rats; Rats, Inbred Lew; Recombinant Proteins - pharmacology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.153.9.4258

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.