Schwann cell-specific regulation of IL-1 and IL-1Ra during EAN: possible relevance for immune regulation at paranodal regions

We reported Schwann cell (SC)-specific autoregulation of IL-1 in vitro [J. Neuroimmunol. 74 (1997a)]. Whether SC resume this autoregulatory potential in vivo and what significance it may have for processes leading to inflamma tion and demyelination of the peripheral nerve remain obscure. Therefore, w e examine SC-specific autoregulation of IL-1 alpha, IL-1 beta and their nat ural antagonist IL-1 receptor antagonist (IL-1Ra) during experimental autoi mmune neuritis (EAN), a model for the human Guillain-Bane syndrome. Autoregulation of IL-1 by SC was analyzed in both, actively induced and ado ptively transferred, EAN. Sciatic nerves were sampled before the onset of c linical signs, 2 to 11 days post immunization (dpi), with P2 peptide, and d uring clinically manifest disease, 11 to 15 dpi. In adoptively transferred EAN, sciatic nerves were analyzed at preclinical stage, 2 to 4 days post P2 peptide-specific cell transfer (dpt) and during clinical manifested phase, 5 to 10 dpt. In both models, IL-1 alpha and IL-1 beta were expressed by SC, during precl inical EAN. IL-1Ra was not detectable in SC at preclinical stage. Further d evelopment and progression to clinically manifest disease was accompanied b y SC-specific expression of IL-1Ra. Although present in other cells in the nerve, IL-1 alpha and IL-1 beta were hardly detectable in SC during clinica l EAN. IL-1Ra immunoreactivity highly co-localized with myelin associated g lycoprotein (MAG), one of the markers for paranodal regions, sites essentia l far proper impulse transmission. Paranodes are also primary sites where a ctivated macrophages make contact with SC, prior to infiltration. SC-specific autoregulation of IL-1 and IL-1Ra is suggestive of its relevanc e for immune regulation at paranodes during EAN. (C) 2001 Elsevier Science B.V. All rights reserved.