Document Detail

Biologic and immunohistochemical analysis of interleukin-6 expression in vivo. Constitutive and induced expression in murine polymorphonuclear and mononuclear phagocytes.
MedLine Citation:
PMID:  1372159     Owner:  NLM     Status:  MEDLINE    
Interleukin-6 (IL-6) is considered an important multifunctional cytokine involved in the regulation of a variety of cellular responses, including the induction of acute-phase protein synthesis, lymphocyte activation, and hematopoiesis. In vitro studies have identified many cells that can produce IL-6, but the cellular sources under physiologic conditions have yet to be identified. Using immunoaffinity purified goat anti-murine IL-6, the authors performed immunohistochemical studies to localize cells expressing IL-6 in selected organs of normal and endotoxin challenged NIH-Swiss outbred mice. In the blood, findings were correlated with cell-associated bioactivity using the standard B9 cell proliferation assay. In normal mice, constitutive expression was seen in granulocytes, monocytes and their precursors as well as in bone marrow and splenic stromal macrophages. Hepatic macrophages were negative, as were lymphocytes, megakaryocytes, erythroid precursors, and endothelial cells. In the absence of significant serum levels of IL-6, cell-associated IL-6 bioactivity was detected in circulating polymorphonuclear leukocytes (PMNs), but not lymphocytes. After endotoxin challenge, there was a threefold increase in PMN IL-6 content from 1 to 3 hours followed by almost complete depletion at 6 hours. This correlated well with a threefold increase of IL-6 mRNA in the bone marrow followed by a decrease at 6 hours. This pattern also correlated with serum levels of IL-6, which peaked at 3 hours and dropped significantly by 6 hours. By 24 hours, cell-associated IL-6 showed recovery with no increase in serum levels. In vivo findings showing IL-6 expression in bone marrow macrophages support in vitro studies suggesting a role for IL-6 in hematopoiesis. Furthermore, PMNs as well as macrophages are likely important sources of IL-6 during inflammatory and septic states.
P D Terebuh; I G Otterness; R M Strieter; P M Lincoln; J M Danforth; S L Kunkel; S W Chensue
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  140     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  1992 Mar 
Date Detail:
Created Date:  1992-04-13     Completed Date:  1992-04-13     Revised Date:  2010-09-07    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  649-57     Citation Subset:  AIM; IM    
Department of Pathology, Veterans Affairs Medical Center, Ann Arbor, Michigan 48105.
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MeSH Terms
Bone Marrow / metabolism
Endotoxins / pharmacology
Escherichia coli
Immunohistochemistry / methods
Interleukin-6 / genetics,  metabolism*
Leukocytes / drug effects
Macrophages / metabolism
Monocytes / metabolism
Neutrophils / metabolism
Phagocytes / metabolism*
RNA, Messenger / blood,  metabolism
Reference Values
Staining and Labeling
Tissue Distribution
Grant Support
Reg. No./Substance:
0/Endotoxins; 0/Interleukin-6; 0/RNA, Messenger

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