Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines

Immunity. 2019 Apr 16;50(4):812-831. doi: 10.1016/j.immuni.2019.03.027.


Since the molecular cloning of interleukin-6 (IL-6) in 1986, many other cytokines have been found to share the same signal transducer, gp130, in their receptor complexes. Thus, the IL-6 family of cytokines now consists of ten members. Although some of the family members' functions are redundant as a result of the expression of gp130, there are also functional distinctions between members. The mechanisms that determine functional redundancies and distinctions are not completely understood. Yet, research has clarified the role of IL-6 family cytokines in autoimmune diseases and has led to effective therapies that target them. Here, we review the IL-6 family of cytokines in autoimmune diseases, with a particular focus on the prototypical member IL-6, from the viewpoints of their structure, signaling, and biological features and discuss possible mechanisms of their functional pleiotropy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Cytokines / genetics
  • Cytokines / physiology*
  • Gene Expression Regulation
  • Genetic Pleiotropy*
  • Inflammation / immunology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / physiology
  • Mice
  • Multigene Family / physiology*
  • Protein Subunits
  • Receptors, Cytokine / physiology
  • Receptors, Interleukin-6 / physiology
  • Signal Transduction
  • Structure-Activity Relationship


  • Cytokines
  • IL6 protein, human
  • Interleukin-6
  • Protein Subunits
  • Receptors, Cytokine
  • Receptors, Interleukin-6