Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. 1991

C A Jacobs, and P E Baker, and E R Roux, and K S Picha, and B Toivola, and S Waugh, and M K Kennedy
Department of Immunology, Immunex Research and Development Corporation, Seattle, WA 98101.

To assess the role of IL-1 in the development of experimental autoimmune encephalomyelitis (EAE), the effects of in vivo treatment with IL-1 alpha or an IL-1 antagonist on the clinical course of EAE were evaluated. First, Lewis rats were immunized with guinea pig myelin in CFA and treated for 19 consecutive days with i.p. injections of recombinant human IL-1 alpha. Clinical signs of paralysis in the IL-1 alpha-treated groups were of longer duration and of greater severity compared to placebo injected controls. In addition, more weight loss was observed in the IL-1 alpha-treated groups compared to controls. This enhanced weight loss was not due to IL-1 alpha injections alone as CFA-treated rats injected with IL-1 alpha did not lose weight when compared to placebo injected, CFA-treated controls. Second, soluble mouse rIL-1R (sIL-1R), which binds both IL-1 alpha and IL-1 beta, was given as an IL-1 antagonist. Treatment of guinea pig myelin/CFA immunized rats with sIL-1R for 13 consecutive days significantly delayed the onset of EAE, reduced the severity of paralysis and weight loss, and shortened the duration of disease. Treatment with sIL-1R was most effective in reducing EAE if administered for 15 consecutive days immediately after immunization. Shortened 5-day treatment regimens spanning days 1 to 5, days 6 to 10, or days 11 to 15 after immunization were less effective in reducing EAE. These data suggest that IL-1 may initiate or promote inflammation within the central nervous system. In addition, specifically blocking the biological activity of IL-1 in vivo by soluble receptors may prove beneficial for the treatment of autoimmune or inflammatory diseases.

UI MeSH Term Description Entries
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D011917 Rats, Inbred Lew An inbred strain of rat that is used in BIOMEDICAL RESEARCH. Rats, Inbred Lewis,Rats, Lew,Inbred Lew Rat,Inbred Lew Rats,Inbred Lewis Rats,Lew Rat,Lew Rat, Inbred,Lew Rats,Lew Rats, Inbred,Lewis Rats, Inbred,Rat, Inbred Lew,Rat, Lew
D011971 Receptors, Immunologic Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere. Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D004681 Encephalomyelitis, Autoimmune, Experimental An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5) Autoimmune Encephalomyelitis, Experimental,Encephalomyelitis, Allergic,Encephalomyelitis, Experimental Autoimmune,Allergic Encephalomyelitis,Allergic Encephalomyelitis, Experimental,Autoimmune Experimental Encephalomyelitis,Experimental Allergic Encephalomyelitis,Experimental Autoimmune Encephalomyelitis,Encephalomyelitis, Autoimmune Experimental,Encephalomyelitis, Experimental Allergic,Experimental Allergic Encephalomyelitides,Experimental Encephalomyelitis, Autoimmune
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001327 Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Autoimmune Disease,Disease, Autoimmune,Diseases, Autoimmune
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D017472 Receptors, Interleukin-1 Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88. IL-1 Receptor,IL-1 Receptors,IL1 Receptor,Interleukin-1 Receptor,Interleukin-1 Receptors,Receptor, Interleukin-1,Receptors, IL-1,IL1 Receptors,Interleukin 1 Receptor,IL 1 Receptor,IL 1 Receptors,Interleukin 1 Receptors,Receptor, IL-1,Receptor, IL1,Receptor, Interleukin 1,Receptors, IL 1,Receptors, IL1,Receptors, Interleukin 1

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