Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation

Annu Rev Med. 2020 Jan 27:71:263-276. doi: 10.1146/annurev-med-041818-011649.

Abstract

Interleukin (IL)-11 is upregulated in a wide variety of fibro-inflammatory diseases such as systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease, kidney disease, drug-induced liver injury, and nonalcoholic steatohepatitis. IL-11 is a member of the IL-6 cytokine family and has several distinct properties that define its unique and nonredundant roles in disease. The IL-11 receptor is highly expressed on stromal, epithelial and polarized cells, where noncanonical IL-11 signaling drives the three pathologies common to all fibro-inflammatory diseases-myofibroblast activation, parenchymal cell dysfunction, and inflammation-while also inhibiting tissue regeneration. This cytokine has been little studied, and publications on IL-11 peaked in the early 1990s, when it was largely misunderstood. Here we describe recent advances in our understanding of IL-11 biology, outline how misconceptions as to its function came about, and highlight the large potential of therapies targeting IL-11 signaling for treating human disease.

Keywords: IL-11; IL11; drug target; fibroblast; fibrosis; inflammation; interleukin-11; stroma.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Fibrosis / immunology*
  • Fibrosis / metabolism
  • Fibrosis / pathology
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-11 / immunology*
  • Interleukin-11 / metabolism
  • Interleukin-11 / physiology
  • Interleukin-6 / immunology
  • Kidney Diseases / immunology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Myofibroblasts / immunology
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Pulmonary Fibrosis / immunology
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Recombinant Proteins
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / pathology
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology

Substances

  • Interleukin-11
  • Interleukin-6
  • Recombinant Proteins