Influence of K ⁺ Channel Openers on Interferon-γ Dependent Immune Response in Experimental Allergic Neuritis (Ean)

Abstract

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-y secreting cells (IFN-γ sc) in response to the specific antigen BPM and the T cell mitogen phytohemagglutinin (PHA). BRL 38227 and diazoxide at concentrations of 10-⁵M-10-⁶M and pinacidil at concentrations of 10-⁵M-10-⁷M enhanced the proliferative response to both BPM and PHA. The number of IFN-y 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-y sc than of cultures with low numbers of BPM-reactive IFN-γ sc. The applied K ⁺” channel openers are primarily acting on ATP-sensitivc K ⁺ channels, which have not been found in T cells so far. The drugs may, therefore, excert 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.

Key Words:

• K ⁺ channels
• T lymphocytes
• interfcron-γ
• autoimmune disease