The cytokines of pulmonary fibrosis: Much learned, much more to learn

Cytokine. 2015 Jul;74(1):88-100. doi: 10.1016/j.cyto.2014.11.008. Epub 2014 Dec 24.


Organ fibrosis, the result of exaggerated, persistent, and often irreversible accumulation of extracellular matrix, complicates numerous diseases in all organs and tissues and has particularly serious consequences in the lungs. Abnormally accumulating scar tissue both replaces normally functioning parenchyma and distorts the architecture of unaffected tissue. In the lungs, the fibrotic process often leads to rapid and severe abnormalities in respiratory mechanics and gas exchange properties. There is no confirmed cure, and better therapies are required for treating fibrosis. The development of therapeutic strategies compels a better understanding of the cellular and molecular mechanisms of fibrosis, which are diverse, complex, and redundant. Epithelial injury, oxidative stress, coagulation disturbances, and inflammation are engaged in a complex interplay leading to augmented transformation of several cell types into myofibroblasts and prolonged survival of these extracellular matrix-producing cells. Cytokines are centrally engaged in the homeostatic and pathophysiologic regulation of connective tissue. Furthermore, it appears that identical cytokines are utilized by inflammation, profibrotic mechanisms, and the fibrotic process itself, suggesting that specific targeting or utilization of these cytokines holds therapeutic promise. In this article, we review the wealth of recent knowledge on major cytokines involved in the fibrotic process.

Keywords: Cytokines; Fibrosis; Growth factors; Lung; Myofibroblasts.

Publication types

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

MeSH terms

  • Animals
  • Cytokines / immunology
  • Cytokines / physiology*
  • Extracellular Matrix / metabolism
  • Humans
  • Inflammation
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Pulmonary Fibrosis / etiology*
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / therapy


  • Cytokines
  • Intercellular Signaling Peptides and Proteins