Proc Natl Acad Sci U S A 2003 Feb 18;100(4):1867-72
Pedotti R, DeVoss JJ, Youssef S, Mitchell D, Wedemeyer J, Madanat R, Garren H, Fontoura P, Tsai M, Galli SJ, Sobel RA, Steinman L.
Departments of Neurology and Neurological Science and Pathology, Stanford University Medical Center, Stanford, CA 94305; and Department of Neuroimmunology, Carlo Besta Neurological Institute, 20133 Milan, Italy.
Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc varepsilon receptor 1 (Fc varepsilon RI), and tryptase.
We now demonstrate that, in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), mediated by T helper 1 (Th1) T cells, histamine receptor 1 and 2 (H1R and H2R) are present on inflammatory cells in brain lesions.
Th1 cells reactive to myelin proteolipid protein expressed more H1R and less H2R than Th2 cells.
Pyrilamine, an H1R antagonist, blocked EAE, and the platelet activating factor receptor antagonist CV6209 reduced the severity of EAE.
EAE severity was also decreased in mice with disruption of the genes encoding Ig FcgammaRIII or both FcgammaRIII and Fc varepsilon RI.
Prostaglandin D synthase and tryptase transcripts were elevated in EAE brain.
Taken together, these data reveal extensive involvement of elements of the immune response associated with allergy in autoimmune demyelination.
The pathogenesis of demyelination must now be viewed as encompassing elements of both Th1 responses and "allergic" responses.