| Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats. | |
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MedLine Citation:
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PMID: 11067955 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man. |
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Authors:
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J M Bakker; A Kavelaars; P J Kamphuis; P M Cobelens; H H van Vugt; F van Bel; C J Heijnen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 165 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2000 Nov |
Date Detail:
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Created Date: 2000-11-21 Completed Date: 2000-12-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 5932-7 Citation Subset: AIM; IM |
Affiliation:
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Departments of. Pediatric Immunology and Neonatology, Wilhelmina Children's Hospital of the University Medical Center, and Rudolf Magnus Institute, Utrecht, The Netherlands. j.m.bakker-2@wkz.azu.nl |
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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blood,
immunology* Animals Animals, Newborn / growth & development, immunology* Body Weight / drug effects Cells, Cultured Corticosterone / antagonists & inhibitors, blood Cytokines / biosynthesis, genetics Dexamethasone / administration & dosage*, adverse effects* Disease Susceptibility Encephalomyelitis, Autoimmune, Experimental / blood, epidemiology, immunology*, physiopathology Female Immunosuppressive Agents / administration & dosage, adverse effects Incidence Injections, Intraperitoneal Interleukin-1 / antagonists & inhibitors, biosynthesis Lipopolysaccharides / administration & dosage, antagonists & inhibitors Lymphocyte Activation / drug effects Macrophages, Peritoneal / immunology, metabolism Male RNA, Messenger / biosynthesis Rats Rats, Wistar Severity of Illness Index Spleen / cytology, drug effects, immunology Tumor Necrosis Factor-alpha / antagonists & inhibitors, biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Immunosuppressive Agents; 0/Interleukin-1; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 50-02-2/Dexamethasone; 50-22-6/Corticosterone |
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