From supernatants to cytokines: a personal view on the early history of IL-1, IL-1Ra, TNF and its inhibitor in rheumatology

Arthritis Research & Therapy
Jean-Michel Dayer

Abstract

Long-term cell cultures developed early in the twentieth century allowed identification in their supernatants of biological mediators subsequently defined as migration factors, interferons, lymphokines, monokines, cytokines and interleukins. In rheumatology, early in the 1930s, synovial cell cultures revealed two major distinct populations, i.e. synovial fibroblasts and monocyte-macrophages. Discovery of the interstitial collagenase (MMP-1) and its role in tissue destruction, such as in rheumatoid arthritis (RA), raised the question of the cellular source for this enzyme. My personal interest in the field was driven by the lack of understanding for the link between tissue destruction and immunology. This triggered our seminal contribution to the field, establishing in 1976-79 at the Arthritis Unit (Massachusetts General Hospital, with SM Krane) that a mononuclear factor (MCF, around 15 kDa) produced by stimulated macrophage, under direct contact with activated T cells, induced large amounts of collagenase and prostaglandin E2 (PGE2, a bone resorbing agent) in human synovial fibroblasts from RA patients. Our original "MCF" biological observations preceded cloning, and recombinant IL-1β confirmed the biological activity of the pu...Continue Reading

References

Mar 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·J M DayerD R Robinson
Mar 1, 1990·European Journal of Immunology·G J MazzeiA R Shaw
Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P SeckingerJ M Dayer
Apr 1, 1988·The Journal of Experimental Medicine·P SeckingerJ M Dayer
Feb 1, 1986·The Journal of Clinical Investigation·J M DayerC A Dinarello
Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·S B MizelS E Mergenhagen
Jul 12, 2002·Arthritis Research·Danielle Burger, Jean-Michel Dayer
Jun 15, 1962·Proceedings of the National Academy of Sciences of the United States of America·J GROSS, C M LAPIERE
Nov 20, 2016·Arthritis Research & Therapy·Adam P CroftChristopher D Buckley

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