Role of interleukins in the pathogenesis of pulmonary fibrosis

Yi Xin She, Qing Yang Yu, Xiao Xiao Tang, Yi Xin She, Qing Yang Yu, Xiao Xiao Tang

Abstract

Interleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Interleukins affect the morphology and…
Fig. 1. Interleukins affect the morphology and functions of various cells in pulmonary fibrosis.
(1) Mesenchymal stem cells: IL-8 facilitates the migration and proliferation of mesenchymal stem cells. (2) Macrophages: IL-8 also induces migration of macrophages. IL-4, IL-13, IL-10, and IL-33 promote macrophages to transform into M2 phenotype, which is further promoted by IL-4, IL-6, and IL-13 to transform into a hyper-profibrotic phenotype. (3) Other immune cells: IL-1β induces recruitment of lymphocytes and neutrophils, while IL-5 induces recruitment of eosinophils. (4) Alveolar epithelial cells: IL-17A inhibits autophagy of alveolar epithelial cells, and IL-6 suppresses apoptosis of alveolar type II cells (AT II). IL-6, IL-17A, and IL-18 promote EMT of AT II, whereas IL-22 inhibits this process. (5) Fibroblasts: IL-6 and IL-25 promote the proliferation of fibroblasts. IL-4, IL-11, IL-13, and IL-25 induce differentiation of fibroblasts, whereas IL-27 suppresses both events. IL-18 contributes to the senescence of fibroblasts, and IL-37 facilitates autophagy of fibroblasts. IL-1β, IL-4, IL-6, IL-11, IL-13, IL-17A, IL-25, and IL-33 promote collagen synthesis, while IL-7, IL-12, and IL-27 inhibit collagen synthesis.

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