Dynamics of mRNA expression of interferon-γ, interleukin 4 and transforming growth factor β1 in sciatic nerves and...

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-Barré syndrome. Cytokines including interferon-γ (IFN-γ) have previously been shown to be upmodulated in lymphoid organs and assumed to be involved in the pathogenesis of EAN. Cytokines in the target organ for autoaggressive immunity in EAN, the PNS, could be pivotal for the development of EAN. By adopting in situ hybridization, we studied mRNA expression of the T helper 1 (Th1) cell associated IFN-γ, the Th2 cell related interleukin-4 (IL-4) and the immune response down-regulating TGF-β1 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 myelin (BPM) and Freund's complete adjuvant. The dynamics of IFN-γ mRNA expression in the sciatic nerve followed approximately the clinical course of EAN with peak values around day 14 post immunization (p.i.), whereas IFN-γ was transcribed earlier in the spleen and lymph nodes 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 numbers of TGF-β mRNA positive cells were observed during the clinical improvement of EAN. The data argue for a major proinflammatory role for IFN-γ, and a disease down-regulating function for TGF-β at the target site in EAN.