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Interleukin-1 Mediated Autoinflammation from Heart Disease to Cancer

  • Charles A. DinarelloEmail author
Chapter

Abstract

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.

Keywords

Inflammation Cytokines Osteoarthritis Cancer Heart Atherosclerosis Biologics Anakinra Canakinumab 

Abbreviations

3-MCA

3-methylcholanthrene

AOSD

Adult-onset Still disease

BMI

Body mass index

CANTOS

Canakinumab Anti-inflammatory Thrombosis Outcomes Study

CAPS

Cryopyrin-associated periodic syndrome

CRP

C-reactive protein

CSF

Cerebrospinal fluid

CTLA-4

Cytotoxic T-lymphocyte-associated protein 4

FMF

Familial Mediterranean fever

HER2

Human epidermal growth factor receptor 2

IL

Interleukin

IL-1R1

IL-1 receptor 1

IL-1Ra

IL-1 receptor antagonist

LBM

Lean body mass

MABp1

Monoclonal antibody p1

MCD-1

Macrophage-derived chemoattractant-1

MDSC

Myeloid-derived suppressor cells

NIHSS

National Institutes of Health stroke scale

NK

Natural killer

NLRP3

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

NOMID

Neonatal-onset multisystem inflammatory disease

PD-1

Programmed cell death protein 1

STEMI

ST-elevated myocardial infarction

TAM

Tumor-associated macrophages

TNF

Tumor necrosis factor

TRAPS

TNF receptor-associated periodic syndrome

WT

Wild type

Notes

Acknowledgements

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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