The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

Abstract

Significance: Fibrosis is the endpoint of chronic disease in multiple organs, including the skin, heart, lungs, intestine, liver, and kidneys. Pathologic accumulation of fibrotic tissue results in a loss of structural integrity and function, with resultant increases in morbidity and mortality. Understanding the pathways governing fibrosis and identifying therapeutic targets within those pathways is necessary to develop novel antifibrotic therapies for fibrotic disease. Recent Advances: Given the connection between inflammation and fibrogenesis, Interleukin-10 (IL-10) has been a focus of potential antifibrotic therapies because of its well-known role as an anti-inflammatory mediator. Despite the apparent dissimilarity of diseases associated with fibrotic progression, pathways involving IL-10 appear to be a conserved molecular theme. More recently, many groups have worked to develop novel delivery tools for recombinant IL-10, such as hydrogels, and cellbased therapies, such as ex vivo activated macrophages, to directly or indirectly modulate IL-10 signaling. Critical Issues: Some efforts in this area, however, have been stymied by IL-10's pleiotropic and sometimes conflicting effects. A deeper, contextual understanding of IL-10 signaling and its interaction with effector cells, particularly immune cells, will be critical to future studies in the field. Future Directions: IL-10 is clearly a gatekeeper of fibrotic/antifibrotic signaling. The development of novel therapeutics and cell-based therapies that capitalize on targets within the IL-10 signaling pathway could have far-reaching implications for patients suffering from the consequences of organ fibrosis.

The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing

“…Similarly, interstitial pulmonary fibrosis, a progressive condition defined by deposition of scar tissue in the lung interstitium, is caused by post-inflammatory fibrotic reactions. Renal fibrotic diseases, such as crescentic glomerulonephritis, also emphasize the systemic nature of the scar formation processes ( Sziksz et al, 2015 ; Steen et al, 2019 ). Taken in a broader context, it has been postulated that fibrosis accounts for almost 50% of worldwide mortality ( Wynn, 2004 ).…”

What immunological and hormonal protective factors lower the risk of COVID-19 related deaths in pregnant women?

“…The multitude sources of IL-10, particularly at the placental-decidual interface (trophoblasts, uterine natural killer cells, monocytes, and Tg cells), make it to be available in abundant amount ( Thaxton and Sharma, 2010 ), which is a benefit for the dominance of the anti-inflammatory state of pregnancy. The implication is that the anti-inflammatory and antifibrotic actions of IL-10 in the lungs and other tissues by suppressing the Th-1 immunity ( Steen et al, 2020 ) is probably protective from COVID-19. Interestingly, while inhibiting the Th-1 cells, IL-10 enhances B cells survival and antibody production, which is beneficiary to balance the immune suppression and induction ( Matilainen et al, 2010 ).…”

Modulation of the secretion of mesenchymal stem cell immunoregulatory factors by hydrolyzed fish collagen

“…effector cells and the generation of cytotoxic lymphocytes from CD8+ cells, in addition to directly inhibiting T-helper cell differentiation (43). IL-10 is an anti-inflammatory cytokine that can directly inhibit the activation of inflammatory cells, thereby reducing the production of inflammatory cytokines (44). The timely and moderate production of IL-10 has also been discovered to relieve inflammation and protect normal tissues from inflammatory injuries (45).…”