+1 (502) 904-2126   One Westbrook Corporate Center, Suite 300, Westchester, IL 60154, USA   Site Map
ISSN: 2574 -1241

Impact Factor : 0.548

  Submit Manuscript

OpinionOpen Access

Dual Role of Interleukin-37 As an Anti-Inflammatory and A Regulatory Cytokine In EAE Volume 4 - Issue 1

Qi Xin, Lingyun Li, Zhong Huang and Zhangbo Chen*

  • Department of Pathogen Biology and Immunology, Shenzhen University School of Medicine, China

Received: April 13, 2018;   Published: April 25, 2018

Corresponding author: Zhangbo Chen, Department of Pathogen Biology and Immunology, Shenzhen University School of Medicine, Nanhai Avenue 3688, Shenzhen 518060, Guangdong, China

DOI: 10.26717/BJSTR.2018.04.000997

Abstract PDF


Interleukin 37 (IL-37) was known as IL-1F7 before Nold and his colleagues renamed it. Nold believed that IL-37 which expressed on cells including macrophages or epithelial cells plays an anti-inflammatory effect under the condition of intracellular and extracellular. IL-37 almost completely suppresses the production of pro-inflammatory cytokines, whereas the abundance of these cytokines increased with silencing of endogenous IL-37 in human cells [1]. Most studies have now focused on the function of IL-37 as an anti-inflammatory cytokine, while other related functions are still being explored. An autoimmune disease is a condition in which the immune system attacks the body [2,3]. Recent research confirmed that IL-37 is associated with many autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS) [4-7]. These studies have shown that IL-37 could inhibit pro- inflammatory cytokines such as TNF-α, IL-1α, IL-1β, IL-6, G-CSF and GM-CSF [1-3].

In order to verify that IL-37 could inhibit these inflammatory factors in experimental allergic encephalomyelitis model (EAE), which is commonly used as an animal model for studying multiple sclerosis, we constructed an EAE model using IL-37 transgenic mice. We hypothesized that IL-37 could alleviate the pathological symptom by reducing inflammatory factors. We found that IL-37 can increase the expression of anti-inflammatory cytokines such as IL-10 and reduce that of pro-inflammatory factors including GM- CSF, IL-6, TNF-α. However, the clinical symptoms of IL-37 transgenic mice in EAE were more serious. This experiment has been repeated for many times. Nowadays more and more evidences have shown some cytokines play a dual role in pro- and anti-inflammatory activities. For example, granulocyte macrophage colony stimulating factor (GM-CSF) was now considered to be a pro- and antiinflammatory activities with the functional outcome dependent on the dose and the presence of other relevant cytokines in the context of an immune response [8].


We supposed that IL-37 may be able to achieve its antiInflammatory and a regulatory cytokine role by reducing some special dual role pro-inflammatory cytokines. More precise results need to be proved in more experiments.


  1. Nold MF, NoldPetry CA, Zepp JA, Palmer BE, Bufler P, et al. (2010) IL-37 is a fundamental inhibitor of innate immunity. Nat Immunology 11(11): 1014-1022.
  2. NoldPetry CA, Lo CY, Rudloff I, Elgass KD, Li S, et al. (2015) IL-37 requires the receptors IL-18Ra and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunology 16(4): 354-365.
  3. Dinarello CA, NoldPetry C, Nold M, Fujita M, Li S, et al. (2016) Suppression of innate inflammation and immunity by interleukin-37. Eur J Immunol 46(5): 1067-1081.
  4. Wang M, Wang B, Ma Z, Sun X, Tang Y, et al. (2016) Detection of the novel IL-1 family cytokines by QAH-IL1F-1 assay in rheumatoid arthritis. Cell Mol Biol 62(4): 31-34.
  5. Xu WD, Zhao Y, Liu Y (2015) Insights into IL-37, the role in autoimmune diseases. Autoimmun Rev 14(12): 1170-1175.
  6. Tete S, Tripodi D, Rosati M, Conti F, Maccauro G, et al. (2012) IL-37 (IL- 1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation. Int J Immunopathol Pharmacol 25(1): 31-38.
  7. Boraschi D, Lucchesi D, Hainzl S, Leitner M, Maier E, et al. (2011) IL-37: a new anti-inflammatory cytokine of the IL-1 family. Eur Cytokine Netw 22(3): 127-147.
  8. Bhattacharya P, Budnick I, Singh M, Thiruppathi M, Alharshawi K, et al. (2015) Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy. J Interferon Cytokine Res 35(8): 585-599.