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Guillain-Barré syndrome offers the unusual opportunity of investigating the early stages of a monophasic autoimmune response. Créange et al (pp 162–5 of this volume) have shown that the concentration of the immunoregulatory cytokine transforming growth factor (TGF-β1) is decreased in Guillain-Barré syndrome at the time of presentation and increases after treatment with either plasma exchange or intravenous immunoglobulin. These results are in line with a previous report.1 They also confirm the previously reported increased concentrations of the inflammatory cytokine tumour necrosis factor α.2 Circulating concentrations of cytokines may not reflect accurately the events in the endoneurium but these findings are consistent with the presence of the message for and expression of these cytokines in peripheral nerves in experimental autoimmune neuritis.3 The source of the TGF-β1 in Guillain-Barré syndrome is likely to be the endoneurial inflammation, and Créange et al recommend measurement of TGF-β1 to identify the inflammatory nature of a neuropathy. More information is needed about the specificity of such an assay as concentrations are likely to be increased non-specifically in inflammatory conditions and after peripheral nerve or CNS injury. It would also be helpful to know whether raised concentrations of this cytokine represent a response to treatment or the evolution of the disease, and whether they predict a favourable outcome. The cells which produce TGF-β1 include megakaryocytes,4 macrophages, CD8+ T cells, and a subpopulation of CD4+ Th cells. Th1 cells secrete inflammatory cytokines, such as IL-2, interferon-γ, and stimulate cell mediated immunity. Th2 cells produce regulatory cytokines including the interleukins IL-4, IL-5, IL-6, IL-9, and IL-10, which down regulate Th1 cells and enhance B cell responses. In rats treated with oral myelin basic protein to abrogate experimental autoimmune encephalitis, Chenet al have proposed a third category of Th cells: these Th3 cells produce TGF-β1, do not have the cytokine profile of Th1 or Th2 cells, but do have the ability to suppress the autoimmune disease.5 The finding of a decreased TGF-β1 concentration in the blood in the acute phase of Guillain-Barré syndrome does raise challenging questions about the possibility of manipulating the immune response to tip the balance towards immunoregulatory and away from inflammatory cytokines. Immunoregulatory cytokines, including interferon-β, are themselves possible therapeutic agents. When added to lymphocytes in vitro, interferon-β stimulated the production of mRNA message for TGF-β1.6Moreover interferon-β suppressed experimental autoimmune encephalitis, although treatment needed to be continued to prevent rebound disease.7 More information is needed about the time course, role, and effects of cytokines in patients and animal models8 to direct future clinical trials in human inflammatory neuropathy.
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