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

Overview of attention for article published in Arthritis Research & Therapy, May 2018
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Title
From supernatants to cytokines: a personal view on the early history of IL-1, IL-1Ra, TNF and its inhibitor in rheumatology
Published in
Arthritis Research & Therapy, May 2018
DOI 10.1186/s13075-018-1607-y
Pubmed ID
Authors

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 purified natural IL-1. Following my return to Geneva in 1980 and searching for a high level of IL-1 in urine and serum of patients with high fever or Still's disease, to our surprise-"a finding of absence"-we found that IL-1 was masked by a factor of approximately 17 kDa and first presented this in 1984 at the Fourth International Lymphokine Workshop. In 1987, before IL-Ra cloning, my co-worker P Seckinger and I demonstrated first-time observation in cytokine biology that the mechanism was due to the inhibition of IL-1 binding the cell surface receptor, leading to the concept of IL-1 receptor antagonist (IL-1Ra). Having reported in 1985 that TNF/cachectin also induced collagenase and PGE2 in human synovial cells, we found that IL-1Ra did not block TNF-α but was due to another inhibitor. As other investigators, we confirmed that this inhibitory factor was a soluble TNF receptor. The years between the 1970s and 1990s were probably the most exciting period in the field of cytokines and cytokine antagonists; it gave rise to two concepts in the cytokine field-one of the receptor antagonist, and the other of soluble receptor antagonists.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 16%
Other 3 9%
Student > Master 3 9%
Researcher 3 9%
Student > Doctoral Student 2 6%
Other 3 9%
Unknown 13 41%
Readers by discipline Count As %
Medicine and Dentistry 8 25%
Biochemistry, Genetics and Molecular Biology 5 16%
Chemical Engineering 1 3%
Immunology and Microbiology 1 3%
Agricultural and Biological Sciences 1 3%
Other 2 6%
Unknown 14 44%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 June 2018.
All research outputs
#16,053,755
of 25,382,440 outputs
Outputs from Arthritis Research & Therapy
#2,337
of 3,381 outputs
Outputs of similar age
#199,000
of 344,275 outputs
Outputs of similar age from Arthritis Research & Therapy
#44
of 58 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 28th percentile – i.e., 28% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,275 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.