Interleukin-1 Mediated Autoinflammation from Heart Disease to Cancer

  • Charles A. DinarelloEmail author


Interleukin-(IL)-1α and IL-1β are highly active proinflammatory cytokines which lower pain thresholds and damage tissues. Monotherapy blocking IL-1 in hereditary autoinflammatory syndromes results in a rapid and sustained reduction in disease severity. But blocking IL-1 activity is also effective in treating common conditions such as gout and post-myocardial infarction heart failure. Targeting IL-1 in a broad spectrum of new indications is ongoing. There are several trials of IL-1 inhibition in cancer. Initially believed to be contraindicated, targeting IL-1 in cancer has expanded greatly. Anti-IL-1α has been used to treat patients with metastatic lung and colorectal cancers, advanced pancreatic cancer, human epidermal growth factor receptor 2 (HER2) negative breast cancer and with smoldering myeloma. A placebo controlled randomized trial of canakinumab in over 10,000 subjects revealed a marked decrease in the incidence and survival of patients with lung cancer. In each of these cancers, a role for IL-1 mediated autoinflammation is a fundamental mechanism of action.


Inflammation Cytokines Osteoarthritis Cancer Heart Atherosclerosis Biologics Anakinra Canakinumab 





Adult-onset Still disease


Body mass index


Canakinumab Anti-inflammatory Thrombosis Outcomes Study


Cryopyrin-associated periodic syndrome


C-reactive protein


Cerebrospinal fluid


Cytotoxic T-lymphocyte-associated protein 4


Familial Mediterranean fever


Human epidermal growth factor receptor 2




IL-1 receptor 1


IL-1 receptor antagonist


Lean body mass


Monoclonal antibody p1


Macrophage-derived chemoattractant-1


Myeloid-derived suppressor cells


National Institutes of Health stroke scale


Natural killer


Nucleotide-binding domain and leucine-rich repeat pyrin containing 3


Neonatal-onset multisystem inflammatory disease


Programmed cell death protein 1


ST-elevated myocardial infarction


Tumor-associated macrophages


Tumor necrosis factor


TNF receptor-associated periodic syndrome


Wild type



This work was supported in part by NIH Grant AI-15614, the Colorado Cancer Center and National Cancer Institute Grant P30CA046934. The author thanks Dr. Giulio Cavalli for his help with the sections on osteoarthritis and heart disease.


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Authors and Affiliations

  1. 1.Department of MedicineColorado Cancer Center, University of ColoradoAuroraUSA
  2. 2.Department of MedicineRadboud University Medical CenterNijmegenThe Netherlands

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