| Interleukin-6 exacerbates glomerulonephritis in (NZB x NZW)F1 mice. | |
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MedLine Citation:
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PMID: 8178944 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The ability of interleukin-6 (IL-6) to modulate immune parameters and mesangial cell function suggests a role for this cytokine in the development of autoimmune glomerulonephritis. This hypothesis was tested in 6-month-old female (NZB x NZW)F1 mice that were administered recombinant human IL-6 (rhIL-6) (50 and 250 micrograms/kg s.c.) for 12 weeks, resulting in an accelerated and severe form of membranoproliferative glomerulonephritis associated with marked upregulation of mesangial major histocompatibility complex class II antigen and glomerular ICAM-1 expression. To distinguish direct effects of rhIL-6 on the renal mesangium from those mediated through the immune system, (NZB x NZW)F1 mice were immunosuppressed with cyclosporin. Immunosuppression by cyclosporin inhibited the development of glomerulonephritis, decreased class II antigen expression, and abrogated IL-6-mediated effects. Administration of neutralizing anti-IL-6 antibody had no effect on the spontaneous development of glomerulonephritis in (NZB x NZW)F1 mice. This finding, together with undetectable IL-6 serum levels, makes a pathogenetic role of endogenously produced IL-6 in this disease model unlikely. In contrast to (NZB x NZW)F1 mice, parental NZW or BALB/c mice given high doses of rhIL-6 (500 micrograms/kg) or recombinant murine IL-6 (100 micrograms/kg) daily for 4 weeks failed to develop morphological or biochemical evidence of glomerulonephritis. Induction of acute phase proteins, anemia, thrombocytosis, and induction of renal class II antigen confirmed the biological activity of IL-6 in these mice. In conclusion, while non-nephritogenic in normal mice, IL-6 accelerates the development of the genetically determined glomerulonephritis of (NZB x NZW)F1 mice through effects mediated by a modulated immune system. Since neutralizing IL-6 antibody treatment did not prevent the development of glomerulonephritis, it is unlikely that increased IL-6 production plays a role in the pathogenesis of lupus nephritis. |
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Authors:
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B Ryffel; B D Car; H Gunn; D Roman; P Hiestand; M J Mihatsch |
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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: The American journal of pathology Volume: 144 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 1994 May |
Date Detail:
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Created Date: 1994-06-06 Completed Date: 1994-06-06 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 927-37 Citation Subset: AIM; IM |
Affiliation:
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Institute of Toxicology, Faculty of Medicine, University of Zurich, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies / pharmacology Biological Availability Cyclosporine / pharmacology Female Glomerulonephritis / etiology*, mortality, pathology HLA-D Antigens / drug effects, metabolism Interleukin-6 / administration & dosage, adverse effects*, antagonists & inhibitors, metabolism Male Mice Mice, Inbred BALB C Mice, Inbred NZB Microscopy, Electron Proteinuria / etiology Species Specificity Survival Rate |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/HLA-D Antigens; 0/Interleukin-6; 59865-13-3/Cyclosporine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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