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Journal of
Rheumatic Diseases and Treatment
ISSN: 2469-5726
MINI REVIEW | VOLUME 4, ISSUE 1 | OPEN ACCESS DOI: 10.23937/2469-5726/1510058

The Role of Interleukin-37 in Inflammation: Suppression or Promotion?

Liping Ding, Xiaoping Hong and Dongzhou Liu

Department of Rheumatology and Immunology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China

*Corresponding author: Dongzhou Liu, Department of Rheumatology and Immunology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China, E-mail: liu_dz2001@sina.com

Received: September 06, 2017 | Accepted: January 20, 2018 | Published: January 22, 2018

Citation: Ding L, Hong X, Liu D (2018) The Role of Interleukin-37 in Inflammation: Suppression or Promotion?. J Rheum Dis Treat 4:058. doi.org/10.23937/2469-5726/1510058

Copyright: © 2018 Ding L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

We read with great interest the paper presented in the current issue of the Journal of innate immunity by Schauer, et al. [1] showing the pathogenic role of Interleukin-37 (IL-37) in the murine model of Streptococcus pneumoniae pneumonia. This study found that recruitment of alveolar macrophages and neutrophils was markedly increased in the mice transgenic for human IL-37b (IL-37tg) with heavier pneumococcal burden, resulting in necrotizing pneumonia with augmented death of infiltrating neutrophils, and leading to enhanced inflammation, tissue damage, and mortality. However, several published studies displayed IL-37tg mice had less severe inflammation in models of endotoxin shock, colitis, obesity-induced inflammation and myocardial inflammatory [2-5]. The authors argued that it is mainly due to the core components of a successful inflammatory response to pneumococcal pneumonia, which lead to increased inflammation, tissue damage, and mortality and is modulated by IL-37 cytokine [1].

However, recent studies have suggested that IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. In vivo, IL-37 exhibited anti-inflammatory activity in murine models of dextran sulfate sodium-induced colitis, monosodium urate crystal-induced inflammation, psoriasis, myocarditis, rheumatoid arthritis and airway inflammation [6-11]. IL-37 not only has anti-inflammatory effects, but also induces marked metabolic changes with higher levels of muscle AMPK, greater rates of oxygen consumption, and increased oxidative phosphorylation both in the context of inflammation- induced fatigue and in healthy mice [12]. In addition, expression of human IL-37 in mice could protect cardiomyocytes from apoptosis and suppress the migration ability of neutrophils in myocardial ischaemia/reperfusion injury condition [13]. Administration of IL-37 to the mice which subjected to endotoxin or high fat diet could attenuate aortic valve thickening and control the progression of calcific aortic valve disease [14]. Previous studies have shown that IL-37 has therapeutic potential for these mouse models of human disease.

IL-37 has been found to increase and restrain the pro-inflammatory cytokine production in various diseases associated with inflammation, including Tuberculosis, Behçet's disease, Acute coronary syndrome, Graves' disease, Ankylosing Spondylitis and Erosive osteoarthritis [15-20]. These findings further suggest an immunosuppressive role of IL-37 in the pathogenesis of autoimmune inflammation by downregulating pro-inflammatory cytokines. Proteomic and transcriptomic investigations revealed that the anti-inflammatory properties of IL-37 require the receptors IL-18Rα and IL-1R8 (SIGIRR) to harness the signaling molecules Mer, PTEN, STAT3 and p62(dok), and further suppress the kinases Fyn and TAK1 and the transcription factor NF-κB, as well as MAPK [21].

In conclusion, we agree with Schauer's statement that IL-37tg mice could develop excessive inflammation and tissue damage when faced with S. pneumoniae infection. However, we believe that IL-37, as anti-inflammation cytokine, is involved in various diseases with inflammation, at least in humans. As autoimmune and infectious diseases share common characteristics in the inflammatory responses, improved understanding of the role of IL-37 in humans with autoimmune diseases or infections may have significant implications for identifying IL-37 as a biomarker for disease progress and therapeutic target.

Acknowledgments


This work was supported by grants Sanming project of medicine in Shenzhen, the group of Rheumatology and Immunology leaded by Xiaofeng Zeng of Peking Union medical college Hospital and Dongzhou Liu in Shenzhen People's Hospital (SYJY201704 and SYJY201705); Shenzhen science and technology research Foundation (JCYJ20160422154407256), Shenzhen technology development project (CXZZ2015093010522591) and Shenzhen Health Plan Committee Research Foundation (201601014), China Postdoctoral Science Foundation (2017M622911).

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