Effect of ion channel blockers on immune response and course of experimental allergic neuritis.
The influence of the K+ channel blocker quinidine and the Ca++ channel blocker verapamil on in vivo and in vitro immune responses was tested in experimental allergic neuritis (EAN) of Lewis rats. Daily intraperitoneal injections of 4 mg quinidine produced a significant reduction of neurological deficits in EAN rats, whereas verapamil had no effect. In contrast, both drugs inhibited the in vitro proliferative response of regional lymph node cells to specific antigens of bovine peripheral myelin and purified protein derivative of tuberculin in a similar dose-dependent manner. Quinidine-treated EAN rats revealed considerably less inflammatory infiltration in target tissue than untreated EAN rats, shown immunohistochemically. Single injections of ion channel blockers into EAN rats did not improve nerve cell functions as measured by electrophysiological recordings of sciatic nerve. It is concluded that the dominant effect of quinidine in vivo is attributed to a reduction of the demyelinating autoimmune process. Hence ion channel blocking drugs can exert immunomodulatory effects, which may have implications for their clinical application.
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Department of Neurology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
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D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects*; D008214:Lymphocytes / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D011802:Quinidine / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology*
D007473:Ion Channels; D014700:Verapamil; D011802:Quinidine