Role of IL-10 in the Resolution of Airway Inflammation

Abstract

IL-10 can be considered an important agent in the resolution of inflammation. Originally named "cytokine synthesis inhibitory factor" for its ability to inhibit IFN-gamma and IL-2 production in Th2 cells, it is secreted by monocytes, macrophages, mast cells, T and B lymphocytes, and dendritic cells (DCs). IL-10 production and release by monocytic cells in response to allergic challenge is upregulated by TNF-alpha, and by negative feedback regulation of itself. However, it is also secreted by T regulatory cells (Tregs), under the control of IL-2. Importantly in the context of asthma, IL-10 inhibits eosinophilia, by suppression of IL-5 and GM-CSF, by direct effects on eosinophil apoptosis, and effects on cell proliferation through down-regulation of IL-1. A number of its cytokine suppressive characteristics are now thought to occur through its upregulation of suppressor of cytokine signaling (SOCS)-3. IL-10 is also a suppressor of nitric oxide (NO) production, which may have ramifications for its role in airway inflammatory diseases. Initial clinical trials have demonstrated relative safety and few clinically adverse events at doses of recombinant human IL-10 below 50 microg/kg, with mixed success in treatment of patients with inflammatory bowel disease and psoriasis. However, both steroid therapy and allergen specific immunotherapy are known to elevate endogenous IL-10 levels, which may account for their efficacy, suggesting that further study of IL-10 as a target for treatment of airway inflammatory diseases such as asthma and COPD is warranted.

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

“…Moreover, in our study the levels of the antiinflammatory IL-10 were significantly increased in the OVA-CdM lungs, suggesting that BMC CdM attenuates allergic T H 2 inflammation through an IL-10-dependent mechanism. IL-10 has been shown to contribute to the reduction of airway inflammation (40). BMC CdM itself acted as an exogenous source of IL-10; however, we did not find a significant difference between the levels of IL-10 in the lungs of BMC CdM-treated control animals and untreated controls, suggesting that endogenous production of IL-10 in the allergic inflammatory environment may be an important component of elevated IL-10 levels found only in OVA-CdM lungs.…”

“…It is therefore possible that administration of BMC CdM would induce the Tr1 through IL-10 found in the CdM with a similar, simultaneous up-regulation of IL-10 production by lung macrophages through APN. This would lead to a sustained production of endogenous IL-10 that may contribute to attenuation of inflammatory events (40).…”

Intranasal CpG Therapy Attenuated Experimental Fungal Asthma in a TLR9-Dependent and -Independent Manner

“…Changes in IL-10 following IN CpG were also TLR9 dependent. The inhibitory effects of IL-10 on allergic inflammation are well known and include regulation of eosinophilia [8], inhibition of the proliferation of various structural cell types [41], and regulation of airway inflammation through its inhibitory action on nitric oxide, a potent mediator of AHR [42,43]. Recent studies have shown that the adoptive transfer of IL-10-overexpressing DCs into OVA-sensitized and challenged mice ameliorates allergic asthma symptoms [44].…”

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

“…During asthma, IL-10 can inhibit eosinophilia via suppression of IL-5 and GM-CSF, regulate eosinophil apoptosis, and down-regulate IL-1. In addition, IL-10 can suppress nitric oxide production, an important component of airway inflammation [99]. Upregulation of IL-10 was also demonstrated to normalize blood pressure and endothelial function [100,101].…”