Influence of K+ channel openers on interferon-gamma dependent immune response in experimental allergic neuritis (EAN).
We examined the influence of the K+ channel opening drugs BRL 38227, pinacidil and diazoxide on cellular immune response and clinical course of experimental allergic neuritis (EAN) actively induced in Lewis rats by bovine peripheral myelin (BPM). T cell functions of EAN lymph node cells were assessed by measurement of proliferation and by counting of interferon-gamma secreting cells (IFN-gamma sc) in response to the specific antigen BPM and the T cell mitogen phytohemagglutinin (PHA). BRL 38227 and diazoxide at concentrations of 10(-5)M-10(-6)M and pinacidil at concentrations of 10(-5)M-10(-7)M enhanced the proliferative response to both BPM and PHA. The number of IFN-gamma sc was suppressed by the K+ channel openers in the same concentration range. There was a tendency of stronger suppression of cultures with high numbers of BPM-reactive IFN-gamma sc than of cultures with low numbers of BPM-reactive IFN-gamma sc. The applied K+ channel openers are primarily acting on ATP-sensitive K+ channels, which have not been found in T cells so far. The drugs may, therefore, exert non-selective effects on conventional voltage- and/or Ca(++)-dependent channels of T cells. A first trial with in vivo administration of 2.5 mg/kg x day of the drugs resulted in more severe neurological deficits in the early phase of EAN with BRL 38227, whereas pinacidil and diazoxide had no significant effects.
Mix
E
E
Karolinska Institute, Department of Neurology, Huddinge University Hospital, Sweden.
Zhu
J
J
Olsson
T
T
Link
H
H
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D003981:Diazoxide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D020110:Pinacidil; D007371:Interferon-gamma; D003981:Diazoxide