Life style drugs and immune–mediated peripheral neuropathy

Abstract

Despite rapid progress of therapeutic options for immune–mediated neuropathy (IMN), severe neurological sequelae or intractability still exist. These interfere patients' activity of daily living (ADL) and quality of life (QOL). Life style–related diseases such as hypertension and hyperlipidemia are very common, wide variety of medicines are subscribed daily for those suffering from life style–related diseases (life style drug).

Hydroxymethylglutaryl–CoA reductase inhibitors (statins) and angiotensin II receptor blockers (ARBs), popular life style drugs, additionally exhibit immune suppression ; firstly in animal model of multiple sclerosis although their effects of IMN remain vague. Thus we attempted to investigate the effect of atorvastatin (ATO), one of statins, on EAN. ATO suppressed motor paralysis of EAN mildly and intraneural expression of proinflammatory cytokine interferon–gamma (IFN). Besides, peak of anti–inflammatory cytokine interleukin (IL)–10 expression was also suppressed and delayed. We supposed that ATO might only suppress IFN, not upregulate IL–10, finally suppressed EAN. We then investigated the effect of various ARBs, candesartan (CAN), losartan (LO) and irbesartan (IRB) on EAN. IRB suppressed motor paralysis through entire EAN course while CAN did not suppress and LO delayed onset and accelerated recovery mildly. These differences clearly depended on the affinity to C–C chemokine receptor 2b that is main receptor for C–C chemokine CCL2 which attracts mononuclear phagocytes from blood stream to site of inflammation in peripheral nerve. These affinities can be estimated according to molecular data easily now a days.

Furthermore, in vivo experiments proved the efficacy and accuracy of the molecular modelling. This strategy might be powerful tool to identify unique drugs, formerly off–label common drug such as life style drugs.