Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases

By C. A. Dinarello, A. Simon, J. van der Meer. Nature reviews. Drug discovery, 2012

1,758 citations recorded by the source corpus.

Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.

Subfields: Hematology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cdb69cb7c43ef5bb0806614c41e9b34699319610

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hematology

1. A. Mantovani
2. C. Garlanda
3. M. Lamkanfi
4. C. A. Dinarello

In Immunology

1. C. Garlanda
2. A. Mantovani
3. M. Lamkanfi
4. V. Dixit
5. C. A. Dinarello
6. C. Serhan
7. G. van Loo
8. A. Sica

In Molecular Biology

1. M. Lamkanfi
2. A. Mantovani
3. V. Dixit
4. C. Garlanda
5. C. A. Dinarello
6. C. Serhan
7. G. van Loo
8. H. D. Alexander

Citations in the corpus

• Mechanisms and functions of inflammasomes. (2014, background): “Several other molecules targeting either IL-1b or IL-1R are currently under development (Dinarello et al., 2012).”
• THE INTERLEUKIN-1 FAMILY: BACK TO THE FUTURE (2013, positive): “IL-1 affects virtually all cells and organs and is a major pathogenic mediator of autoinflammatory, autoimmune, infectious, and degenerative diseases (Dinarello, 2009, 2010; Dinarello et al., 2012; Gabay et al., 2010; Sims and Smith, 2010) (Table 2).”
• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “IL-1 gene variants appear to increase the risk of age-related diseases and recombinant drugs, such as IL-1Rα-blockers may have a role in the clinical control of inflammation (164).”
• Pro-resolving lipid mediators are leads for resolution physiology (2014, background): “coli phagocytosis in a phosphatidylinositol-3-OH kinase (PI(3)K)- and scavenger receptor-dependent manner, and ALX/FPR2 is upregulated in patients with Crohn’s disease and enhances bacterial clearance(63).”
• Inflammasomes in neuroinflammatory and neurodegenerative diseases (2019, background): “In agreement, mice deficient in both IL-1a and IL-1b exhibited dramatically reduced ischemic infarct volumes in transient MCAO (Boutin et al, 2001), whereas IL-18-deficient mice did not show protection in this model (Wheeler et al, 2003).”