WESTPORT, CT (Reuters Health) Dec 12 - Mice deficient in complement resist the myelin damage and clinical signs of experimental allergic encephalomyelitis, a model of multiple sclerosis, according to a report in the November 15th issue of the Journal of Immunology.
Recent studies suggest a role for complement in antibody-dependent experimental allergic encephalomyelitis in rats, the authors note. To investigate, Dr. Scott R. Barnum, from the University of Alabama at Birmingham, and colleagues studied myelin oligodendrocyte glycoprotein (MOG)-induced experimental allergic encephalomyelitis in mice lacking C3 or factor B and in wild-type mice.
All control animals developed clinical signs of encephalomyelitis an average of 11 days post-immunization, the report indicates, whereas only one of six C3-deficient mice and two of eight factor B-deficient mice showed any signs of the disease. Moreover, the deficient mice experienced significantly milder disease than their wild-type counterparts.
Unlike the histological appearance in wild-type mice with experimental allergic encephalomyelitis mice, both C3-deficient and factor B-deficient mice showed virtually no parenchymal infiltration and only mild or no myelin damage, the researchers noted. In addition, deficient mice showed markedly fewer infiltrating CD3+ T cells than did control mice.
"The fact that few infiltrating cells were found in the parenchyma of the complement-deficient animals suggests that their protective defect might be reduced production of C3a and/or C5a, which would otherwise direct the recruitment of inflammatory cells from the meninges and/or the perivascular cells to the parenchyma," the investigators propose.
"There is still intensive research ongoing in the area of multiple sclerosis, and it is likely that as the mechanisms underlying the disease are further unraveled, new promising therapeutics approaches will be developed," Dr. Barnum told Reuters Health. "Because of the complexity of the disease, I would predict that combination therapy is likely."
J Immunol 2000;165:5867-5873.
2000 Reuters Ltd.