Tumor necrosis factor-alpha, lymphotoxin, interleukin (IL)-6, IL-10, IL-12 and perforin mRNA expression in mononuclear cells in response to acetylcholine receptor is augmented in myasthenia gravis.
Myasthenia gravis (MG) is a neuromuscular disorder mediated by autoantibodies against the nicotinic acetylcholine receptor (AChR) on the postsynaptic membrane of the neuromuscular junction. The production of antibodies is regulated by T cells by means of immunoregulatory cytokines. To investigate the involvement of TNF-alpha, lymphotoxin (LT), IL-6, IL-10, IL-12 and perforin in MG, numbers of cytokine mRNA expressing blood mononuclear cells (MNC) were examined in patients with MG and controls. LT belongs to the Th1 cell related cytokines, IL-6 and IL-10 to the Th2 type, TNF-alpha is produced by both Th1 and Th2 cells, IL-12 induces T cell switch towards the Th1 type and perforin is an effector molecule inducing cell lysis. Short term culture of MNC with AChR revealed augmented levels of AChR-reactive TNF-alpha, LT, IL-6, IL-10, IL-12 and perforin mRNA expressing cells in MG compared to levels obtained without AChR or in presence of control antigen. AChR-reactive TNF-alpha, IL-6, IL-10, IL-12 and perforin mRNA expressing cells were higher in MG than controls. These findings suggest that the cytokines TNF-alpha, LT, IL-6, IL-10 and IL-12, and the cytolytic effector molecule perforin are also involved in MG.
Matusevicius
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Division of Neurology, Karolinska Institute, Huddinge Hospital, Sweden.
Navikas
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Palasik
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Pirskanen
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Fredrikson
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Link
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D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007378:Interleukins / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D009422:Nervous System Diseases / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D007378:Interleukins; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin