Immunopathogenesis of rheumatic diseases in the context of neuroendocrine interactions.
Growing evidence supports the hypothesis that alterations of the stress response and interactions between the neuroendocrine and immune systems contribute to the pathogenesis of rheumatic diseases such as rheumatoid arthritis (RA). In particular, the hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are of special interest. Polymorphisms of the corticotropin-releasing hormone (CRH)-regulating region have been described recently. These polymorphisms are differentially distributed in RA patients and healthy subjects of various ethnic origin, thus supporting the hypothesis that they represent a new genetic marker for RA susceptibility. The decreased expression of beta(2)-adrenergic receptors (beta(2)-R) on lymphatic cells in rheumatic diseases like RA, together with an impaired influence of catecholamines on immune function in these patients, further underlines the concept of a dysfunction of the ANS in rheumatic diseases. Results from work in this field will provide more insight into the pathogenesis of RA and help to establish novel therapies for this chronic rheumatic disease.
University Hospital Leipzig, Department of Medicine IV, Leipzig, Germany. wahm@medizin.uni-leipzig.de
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Wahle
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Krause
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Pierer
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Hantzschel
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Baerwald
D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D015536:Down-Regulation; D005006:Ethnicity; D020022:Genetic Predisposition to Disease; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects; D008221:Lymphoid Tissue / Q000294:innervation; D008954:Models, Biological; D015213:Neuroimmunomodulation / Q000502:physiology*; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012216:Rheumatic Diseases / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology
D002395:Catecholamines; D018343:Receptors, Adrenergic, beta-2; D003346:Corticotropin-Releasing Hormone