DYNAMICS OF MESSENGER-RNA EXPRESSION OF INTERFERON-GAMMA, INTERLEUKIN-4 AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN SCIATIC-NERVES AND LYMPHOID ORGANS IN EXPERIMENTAL ALLERGIC NEURITIS

Experimental allergic neuritis (EAN) is a T cell mediated inflammatory demyelinating disorder of the peripheral nervous system (PNS) and an animal model of the Guillain-Barre syndrome, Cytokines including inter feron-gamma (IFN-gamma) have previously been shown to be upmodulated i n lymphoid organs and assumed to be involved in the pathogenesis of EA N. Cytokines in the target organ for autoaggressive immunity in EAN, t he PNS, could be pivotal for the development of EAN, By adopting in si tu hybridization, we studied mRNA expression of the T helper 1 (Th1) c ell associated IFN-gamma, the Th2 cell related interleukin-4 (IL-4) an d the immune response down-regulating TGF-beta 1 in the sciatic nerve and, in parallel, in the lymph nodes and the spleen over the course of EAN actively induced by immunization with bovine peripheral nerve mye lin (BPM) and Freund's complete adjuvant. The dynamics of IFN-gamma mR NA expression in the sciatic nerve followed approximately the clinical course of EAN with peak values around day 14 post immunization (p.i.) , whereas IFN-gamma was transcribed earlier in the spleen and lymph no des with maximum on day 7 p.i, In contrast, transcription of IL-4 was only slightly enhanced in EAN, with minor fluctuations in the sciatic nerve peaking on days 11 and 28 p,i. in the lymph nodes, the highest n umbers of TGF-beta mRNA positive cells were observed during the clinic al improvement of EAN, The data argue for a major proinflammatory role for IFN-gamma, and a disease down-regulating function for TGF-beta at the target site in EAN.