History of IL-1
As scientists begin to better understand the functions of the immune system, they are gaining nuanced insights into the progression of disease and the role of immune modifiers. Although one modifier of immune response, interleukin-1 (IL-1), was among the first cytokines or cell signaling molecules described, recent research has opened up a world of possibilities for targeting IL-1 in the treatment of Type-2 diabetes, rheumatoid arthritis, Muckle-Wells syndrome, systemic juvenile idiopathic arthritis (sJIA) and other diseases.
IL-1 Timeline
1940s
Paul B. Beeson identifies substances in blood that influence the development of fever; these substances are later identified as cytokines, most notably interleukin-1
1972
Gery and Waksman described a product present in supernatants of stimulated macrophages that augmented the activation of T lymphocyte responses – leukocyte activation factor (LAF)
1974
Murphy, Chesney and Wood first reported the physical characteristics of a purified form of Endogenous Pyrogen (EP)
1974
Dinarello characterizes two distinct endogenous pyrogens with similar physiological activity; they would later be determined to be IL-1a and IL-1b
1977
Dinarello, Renfer and Wolff purified EP to homogeneity; Kampschmidt and colleagues found that it had biologic activities other than central fever induction; EP and LAF were found to be closely related
1977-1981
Further features of this molecule described – acute-phase-inducing properties. Rosenwasser and Rosenthal showed that highly purified EP was active in the LAF assay
1980
Scientists determine that endogenous pyrogen, leukocyte activating factor and leukocyte endogenous mediator are the same protein
1984-1985
Cloning of IL-1a and IL-1b genes; subsequent sequence analysis and X-ray crystallography demonstrated that IL-1a and IL-1b are distinct proteins with similar structures
1991-1992
Isolation of a naturally produced inhibitor of IL-1 from the serum of experimental models of fever induction – IL-1 Receptor antagonist (IL-1Ra)
November 1999
Amgen presents data on its recombinant IL-1ra compound Kineret at the American College of Rheumatology demonstrating that Kineret combined with methotrexate in rheumatoid arthritis patients demonstrated a meaningful clinical response
December 2000
Regeneron starts clinical trials of its IL-1 Trap (rilonacept) for rheumatoid arthritis
November 2001
Approval of Kineret, recombinant form of the IL-1Ra, for the treatment of rheumatoid arthritis
June 2005
Regeneron announces positive clinical results of its IL-1 Trap (rilonacept) for the treatment of cryopyrin-associated periodic syndromes (CAPS)
April 2007
New England Journal of Medicine paper published demonstrating that an IL-1 blocker can offer significant improvements in blood glucose levels and markers of inflammation in type-2 diabetes patients
July 2007
XOMA commences Phase 1 clinical trials in Type 2 diabetes for its monoclonal antibody IL-1b blocker XOMA 052
February 2008
Approval of ARCALYST™ (rilonacept) for the treatment of CAPS
April 2008
Novartis presents positive Phase II clinical trial results for its IL-1β blocker, ACZ885, for the treatment of CAPS
September 2008
XOMA to announce data for XOMA 052 in Type-2 diabetes at the European Association for the Study of Diabetes
