Document Detail

The process of identifying and understanding cytokines: from basic studies to treating rheumatic diseases.
MedLine Citation:
PMID:  15123036     Owner:  NLM     Status:  MEDLINE    
This is a historical overview seen from a personal angle. It covers the insights made during the past 20 years into the destructive processes of rheumatoid arthritis (RA) related to cytokines. The biochemical knowledge of the matrix components (i.e. collagen) and enzymology (i.e. collagenase) available in the 1950s led to the identification of cells from synovial tissue producing collagenase (fibroblast-like cells) and their interaction with other immune cells, i.e. monocyte-macrophages (Mphi) and lymphocytes (1976-1979). This insight led to the isolation of soluble factors produced by Mphi, such as interleukin-1 (IL-1) and TNF, the principal cytokines inducing collagenase and PGE(2) in many target cells (i.e. synovial fibroblasts, chondrocytes, bone-derived cells) (1981-1985). Further advances resulted from observations that, in clinical conditions (i.e. leukaemia, juvenile RA), a remission of fever and inflammation may occur spontaneously and that tissue catabolism may persist despite the absence of systemic inflammation; this gave rise to the concept and identification of endogenous cytokine inhibitors (i.e. IL-1 receptor antagonist and TNF soluble receptor) (1984-1989). The fourth milestone was the observation that the production of IL-1 and TNF by Mphi was induced mainly by direct contact with lymphocytes, prompting studies of the ligands and counter-ligands on Mphi and lymphocytes as well as inhibitors involved in this cell-cell contact, some of these inhibitors being involved in lipid metabolism and acute-phase proteins (HDL-apo A-1).
Jean-Michel Dayer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Best practice & research. Clinical rheumatology     Volume:  18     ISSN:  1521-6942     ISO Abbreviation:  Best Pract Res Clin Rheumatol     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-05-04     Completed Date:  2004-05-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101121149     Medline TA:  Best Pract Res Clin Rheumatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  31-45     Citation Subset:  IM    
Division of Immunology and Allergy, University Hospital, 24, Rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.
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MeSH Terms
Acute-Phase Proteins / drug effects,  metabolism
Cells, Cultured
Cytokines / drug effects*,  metabolism*
Receptors, Interleukin-1 / metabolism*
Research Design
Rheumatic Diseases / drug therapy*,  immunology,  pathology*
Sensitivity and Specificity
Synovial Membrane / enzymology,  metabolism
Tumor Necrosis Factor-alpha / drug effects,  metabolism
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Cytokines; 0/Receptors, Interleukin-1; 0/Tumor Necrosis Factor-alpha

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