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. 2017 May 23:8:293.
doi: 10.3389/fphar.2017.00293. eCollection 2017.

A Brief History of IL-1 and IL-1 Ra in Rheumatology

Jean-Michel Dayer  1 , Francesca Oliviero  2 , Leonardo Punzi  2
Affiliations

A Brief History of IL-1 and IL-1 Ra in Rheumatology

Jean-Michel Dayer et al. Front Pharmacol. .

Abstract

The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra) in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as "inflammasome" have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still's disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet's disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.

Keywords: autoinflammatory diseases; inflammasome; interleukin-1 antagonist; interleulin-1; rheumatoid arthritis.

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Figures

FIGURE 1
FIGURE 1
Seminal observation about the link between matrix degradation and the biological function of inflammatory molecules produced by immune cells (1976–1977). (1) Cultures of synovial explants from patients with rheumatoid arthritis release large quantities of collagenase and prostaglandins (PGE2) into the media. Secretion of PGE2 declines more rapidly with respect to collagenase whose levels decline after different passages in culture; (2,3) The addition of monocyte-macrophages or their culture supernatants restored collagenase and PGE2 levels. The soluble factor responsible of this effect was later identified in mononuclear cell factor (MCF).
FIGURE 2
FIGURE 2
From fever of unknown origin to the inflammasome puzzle.
See this image and copyright information in PMC

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