The paradoxical role of IL-10 in immunity and cancer

Mannino, Mark H.; Zhu, Ziwen; Xiao, Hualiang; Bai, Qian; Wakefield, Mark R.; Fang, Yujiang

doi:10.1016/j.canlet.2015.07.009

Cited by 353 publications

(256 citation statements)

References 94 publications

(124 reference statements)

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“…3h-i. Finally, the elevated plasma concentration of IL-10 from PBC patients might indicate that this cytokine was not only influenced by Tregs, but also by Th2, Th17, and other innate immune cells, such as macrophages (Moore et al 2001;Mannino et al 2015;Kumar et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

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Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-β), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-β levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.

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Section: Discussionmentioning

confidence: 99%

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

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“…15 IL-10 is a pleiotropic cytokine, which can favor a shift toward Th2 response in the tumor microenvironment. 16 TAMs release IL-10, 13 and tumor cells themselves also produce IL-10. 17 In a study performed on peripheral blood from 30 patients with PTC and multinodular goiter (MNG) as well as 30 patients with MNG alone, IL-10 circulating levels were higher in PTC associated with goiter compared to MNG alone.…”

Section: Cytokinesmentioning

confidence: 99%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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“…IL-10 inhibits nuclear factor-κB signaling, a key inflammatory pathway, and thus downregulates proinflammatory cytokine expression in its role as an antitumor cytokine (14). Furthermore, in previous studies, IL-10 therapy inhibited colon inflammation and carcinoma, while its deficiency in an experimental murine animal model resulted in bacteria-induced carcinogenesis (30,31).…”

Section: Discussionmentioning

confidence: 99%

“…Despite results suggesting that Th1 is dominant over Th2 immunity in the induction of antitumor responses (30), the current data suggested that CVG served as a Th2 immune-inducer through IL-10-dependent pathways. Similarly, gene therapy utilizing Th2 cytokines, including IL-4, -6 and -10, has been reported to be effective in tumor immunotherapy (19,30,31). Thus, despite increased levels of IL-10 in numerous cancers and its association with poor prognosis (30), CVG may exert its apparent anticancer effects through the beneficial immunomodulatory functions of IL-10, among other mechanistic pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effect of IL-10, as a potent anti-inflammatory cytokine produced by monocytes, mast cells, macrophages and dendritic cells, has been reported in a number of cancers, including melanoma and breast and ovarian cancers, and may occur through its suppression of major histocompatibility complex-I activity and induction of NK-mediated tumor lysis (14,18,19). Furthermore, IL-10 has been identified to suppress the growth and metastasis of tumors by inhibiting the production of angiogenic factors (19,31).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Coriolus versicolor glucan on the stimulation of cytokine production in sarcoma-180-bearing mice

et al. 2017

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Abstract. Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-α and -γ at the doses of 100 (P<0.05) and 200 (P<0.01) mg/kg, but not at 40 mg/kg (P>0.05), when compared with cyclophosphamide treatment, as a positive control. Additionally, cytokine production associated with T helper (Th)2 and Th17 cells was enhanced compared with that of Th1 cytokines, and the immunomodulatory function of CVG appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has promise in supporting cancer therapies.

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The paradoxical role of IL-10 in immunity and cancer

Cited by 353 publications

References 94 publications

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

The immune network in thyroid cancer

Effect of Coriolus versicolor glucan on the stimulation of cytokine production in sarcoma-180-bearing mice

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