The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions

Abstract

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a fundamental role in modulating inflammation and in maintaining cell homeostasis. It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have immunostimulating functions under certain conditions. Given the pivotal role of IL-10 in immune modulation, this cytokine could have relevant implications in pathologies characterized by hyperinflammatory state, such as cancer, or infectious diseases as in the case of COVID-19 and Post-COVID-19 syndrome. Recent evidence proposed IL-10 as a predictor of severity and mortality for patients with acute or post-acute SARS-CoV-2 infection. In this context, IL-10 can act as an endogenous danger signal, released by tissues undergoing damage in an attempt to protect the organism from harmful hyperinflammation. Pharmacological strategies aimed to potentiate or restore IL-10 immunomodulatory action may represent novel promising avenues to counteract cytokine storm arising from hyperinflammation and effectively mitigate severe complications. Natural bioactive compounds, derived from terrestrial or marine photosynthetic organisms and able to increase IL-10 expression, could represent a useful prevention strategy to curb inflammation through IL-10 elevation and will be discussed here. However, the multifaceted nature of IL-10 has to be taken into account in the attempts to modulate its levels.

IL‐10‐induced STAT3/NF‐κB crosstalk modulates pineal and extra‐pineal melatonin synthesis

“…IL-10 and melatonin are pleiotropic molecules that exert context-and cell-dependent stimulatory and/or inhibitory effects upon the immune system. 2,4,35,36 The crosstalk among these signals composes a network of interconnections that coordinate the trimming and intensity of several immunological processes in health, pathophysiological, and pathological conditions.…”

“…The dynamic complexity of the system allows independent local and systemic modulations of melatonin content and, therefore, efficient coordination of physiologic and pathophysiologic processes. IL‐10 and melatonin are pleiotropic molecules that exert context‐ and cell‐dependent stimulatory and/or inhibitory effects upon the immune system 2,4,35,36 . The crosstalk among these signals composes a network of interconnections that coordinate the trimming and intensity of several immunological processes in health, pathophysiological, and pathological conditions.…”

Circulating cytokine dynamics as potential biomarker of response to anti-PD-1 immunotherapy in BRAFwt MM patients

“…The role of IL-10 in tumor pathogenesis is controversial, with some findings showing that IL-10 promotes tumor development, while the other results show that this cytokine inhibits tumor growth and metastasis [35] . In immunosuppressive TME IL-10, produced by cancer cells, MDSCs, TAMs, Treg cells, enhances tumor cell survival, proliferation and metastasis by the inhibition of NK and CTL cells.…”

Multifaceted Effects of Subchronic Exposure to Chlorfenapyr in Mice: Implications from Serum Metabolomics, Hepatic Oxidative Stress, and Intestinal Homeostasis

“…As previous studies have indicated, the upregulation of IL-17a could activate the expression of downstream cytokines related to inflammation, including IL-1, IL-6, IL-8, and IL-22, 49,50 whereas IL-10 played a crucial role in suppressing inflammation production. 51,52 These findings suggest that exposure to chlorfenapyr might exacerbate inflammation by enhancing the expression of the proinflammatory factor IL-17a and reducing the anti-inflammatory factor IL-10, leading to an increase in the expression of inflammatory factors IL-1β, IL-6, and IL-22, and ultimately resulting in the development of intestinal inflammation.…”