IL‐4 is a pleiotropic cytokine and has broad effects on a variety of cells, tissues, organs and their biological activities. It is also a well‐known ‘regulatory’ cytokine to the immune system produced mainly by activated Th2 cells and some other cells. Despite its influences on different organs and metabolic activities, IL‐4 possesses important roles in the immune system and immune responses. Understanding of these specific features of IL‐4 will help the design and development of potential therapeutic strategies against many diseases, including allergy, autoimmune and infectious diseases.

Key Concepts

  • Interleukin‐4 is a pleiotropic cytokine involved in a variety of bio‐physiological activities.
  • Interleukin‐4 is considered as a regulatory cytokine and contributes to the treatment of autoimmune diseases by shifting the Th1/Th2 paradigm as well as inducing other modulatory mechanisms.
  • The time and the amount, as well as the producers and responders of interleukine‐4, determine its effects on the immune reactions.
  • An excessive amount of interleukin‐4 deteriorates Treg‐mediated immune suppression through the enhancement of responder T‐cell survival.
  • The presence of interleukin‐4 at a physiological relevant concentration is beneficial to the suppressive immune responses elicited by regulatory T‐cells.

Keywords: interleukin‐4; Th1/Th2 balance; regulatory cytokine; regulatory T‐cells; autoimmune disease

Figure 1. Pleiotropic effects of IL‐4 on physiological and immunological activities. This figure illustrates the important physiological and immunological features of IL‐4. With the wide expression of IL‐4 receptors, IL‐4 acts widely and differentially on various cells, tissues and organs. In the physiological aspect, IL‐4 supports the integral functions including memory, learning and spatial recognition of the brain. IL‐4 also stimulates the proper growth of muscle cells and activates hepatocytes for liver regeneration. IL‐4 involves in the regulation of lipid metabolism and enhancement of insulin action. In addition to its role in supporting B cell proliferation and class switching, IL‐4 serves as the critical factor for the differentiation Th2 lineage as well as M2 macrophages. Interestingly, IL‐4 takes participate in Treg‐mediated immune suppression in a concentration‐dependent manner. High concentration of IL‐4 endows effector T cells (Teffs) with antiapoptotic activities which in turn counteracts the suppressive mechanisms utilized by Tregs whereas physiological relevant concentration of IL‐4 supports such reactions partly by preservation of the survival and granzyme production in Tregs. Some motifolio templates were utilised for illustration.


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Further Reading

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Yang, Wei‐Cheng, Hwang, Yih‐Shiou, and Shen, Chia‐Rui(Nov 2018) Interleukin‐4. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0028195]