title: Effect of stilbene-type anion channel blockers on the immune response during experimental allergic neuritis (EAN).
abstract: We have studied the role of anion channel gating for the autoimmune response in experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM). The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell function was assessed by measurement of proliferation and by counting of interferon-gamma (IFN-gamma) secreting cells (IFN-gamma-sc) in response to BPM and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of spontaneous proliferative activity as well as of proliferation in response to the antigenic stimulus BPM. In contrast, the drug caused a decrease of proliferation of cells stimulated with PHA. The number of cells induced to IFN-gamma secretion was reduced by SITS. The suppressive effect was dependent on the degree of activity of cells without drugs. Cultures showing high numbers of BPM reactive T cells were more easily suppressed than cultures with low numbers of BPM reactive T cells. Our results suggest that anion channel gating is involved in the triggering of T cells to IFN-gamma secretion. The anion channel signal pathway in lymphocytes could be a target for pharmacological intervention in inflammatory disorders. In the presently used autoimmune model, EAN, the net effect of in vivo treatment with SITS resulted in worsening of clinical signs and increased inflammatory cell infiltration in sciatic nerve, whereas the in vitro conductivity of sciatic nerve was not significantly affected by the drug. Thus anion channel gating seems to regulate activities of immune cells, and drugs with anion channel blocking properties may have effects that enhance autoimmune disease.
authors.affiliation: Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Mix
authors.forename: J
authors.initials: J
authors.lastname: Correale
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: G
authors.initials: G
authors.lastname: Solders
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D013267:Stilbenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D013267:Stilbenes; D005576:Colforsin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid