myelin-basic-protein and linsidomine

NO is involved in the regulation of immune responses. The role of NO in the pathogenesis of experimental allergic encephalomyelitis (EAE) is controversial. In this study, 3-morpholinosydnonimine (SIN-1), an NO donor, was administered to Lewis rats on days 5-7 postimmunization, i.e., during the incipient phase of EAE. SIN-1 reduced clinical signs of EAE compared with those in PBS-treated control rats and was accompanied by reduced ED1(+) macrophages and CD4(+) T cell infiltration within the CNS. Blood mononuclear cells (MNC) obtained on day 14 postimmunization revealed that SIN-1 administration enhanced NO and IFN-gamma production by blood MNC and suppressed Ag- and mitogen-induced proliferative responses. MHC class II, B7-1 and B7-2 were down-regulated in SIN-1-treated EAE rats. Simultaneously, frequencies of apoptotic cells among blood MNC were increased. In vivo, SIN-1 is likely to behave as an NO donor. Administration of SIN-1 induced NO production, but did not affect superoxide and peroxynitrite formation. Enhanced NO production during the priming phase of EAE thus promotes apoptosis, down-regulates disease-promoting immune reactivities, and ameliorates clinical EAE, mainly through SIN-1-derived NO, without depending on NO synthase.

Topics: Adjuvants, Immunologic; Amino Acid Sequence; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, CD; B7-1 Antigen; B7-2 Antigen; Cell Membrane; Cell Movement; Down-Regulation; Drug Administration Schedule; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Histocompatibility Antigens Class II; Immunosuppressive Agents; Injections, Intraperitoneal; Interferon-gamma; Leukocyte Count; Leukocytes, Mononuclear; Lymphocyte Activation; Membrane Glycoproteins; Molecular Sequence Data; Molsidomine; Myelin Basic Protein; Nitric Oxide; Nitric Oxide Donors; Peptide Fragments; Rats; Rats, Inbred Lew; Spinal Cord