Interferon γ, interleukin 4 and transforming growth factor β in experimental autoimmune encephalomyelitis in lewis rats: Dynamics of cellular mrna expression in the central nervous system and lymphoid cells

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Abstract
The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon ‐γ (IFN‐γ), interleukin 4 (IL‐4) and transforming growth factor β (TGF‐β) both in sections of spinal cords and the antigen‐induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63–88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN‐γ, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.), and then gradually decreased concomitant with recovery. Very few IL‐4 mRNA‐expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF‐β did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN‐γ, while TGF‐β may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63–88 reactive T cells showed an interesting time‐dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63–88‐induced production of both IFN‐γ and IL‐4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63–88 induced lymphoid cells to TGF‐β production. Thus, an autoantigen‐specific production of TGF‐β occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.

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