INFLUENCE OF K-GAMMA DEPENDENT IMMUNE-RESPONSE IN EXPERIMENTAL ALLERGIC NEURITIS (EAN)( CHANNEL OPENERS ON INTERFERON)

We examined the influence of the K+ channel opening drugs BRL 38227, p inacidil and diazoxide on cellular immune response and clinical course of experimental allergic neuritis (EAN) actively induced in Lewis rat s by bovine peripheral myelin (BPM). T cell functions of EAN lymph nod e 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 pinac idil at concentrations of 10(-5)M-10(-7)M enhanced the proliferative r esponse 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 BP M-reactive IFN-gamma sc than of cultures with low numbers of BPM-react ive 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, excert non-selective effects on convent ional voltage- and/or Ca++-dependent channels of T cells. A first tria l 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 B RL 38227, whereas pinacidil and diazoxide had no significant effects.