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 inflammation and demyelination of the peripheral nerve remain obscure. Therefore, we examine SC-specific autoregulation of IL-1 alpha, IL-1 beta and their natural antagonist IL-1 receptor antagonist (IL-1Ra) during experimental autoimmune neuritis (EAN), a model for the human Guillain-Bane syndrome. Autoregulation of IL-1 by SC was analyzed in both, actively induced and adoptively transferred, EAN. Sciatic nerves were sampled before the onset of clinical signs, 2 to 11 days post immunization (dpi), with P2 peptide, and during 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 preclinical EAN. IL-1Ra was not detectable in SC at preclinical stage. Further development and progression to clinically manifest disease was accompanied by 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 clinical EAN. IL-1Ra immunoreactivity highly co-localized with myelin associated glycoprotein (MAG), one of the markers for paranodal regions, sites essential far proper impulse transmission. Paranodes are also primary sites where activated macrophages make contact with SC, prior to infiltration. SC-specific autoregulation of IL-1 and IL-1Ra is suggestive of its relevance for immune regulation at paranodes during EAN. (C) 2001 Elsevier Science B.V. All rights reserved.