Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

Abstract

Abstract. Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine.

Dysregulation of microRNA‐657 influences inflammatory response via targeting interleukin‐37 in gestational diabetes mellitus

“…Accumulated data have implicated that IL‐37 plays an important role in regulating both innate and adaptive immune responses (Tawfik, Nasef, Omar, & Ghaly, ; Zhao et al, ). In addition, growing bodies of data have revealed that IL‐37 is capable of suppressing the production of inflammatory cytokines, for instance, tumor necrosis factor‐α (TNF‐α) and IL‐6 (L. Wang, Quan, et al, ; L. Wang, Wang, et al, ). A recent study by Yu et al () has shown the evidence that IL‐37 is reduced in GDM placentas and serum and could protect pregnant women from the development of GDM.…”

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

“…The combined comparison of in silico analysis and in vivo data appear in conflict with regard to the finding that a significant reduction in IL37 expression was observed in PBMCs from MS patients undergoing exacerbation of the disease in the in silico analysis whereas augmented levels of IL37 were observed in the circulation of MS patients suffering an exacerbation. These apparently conflicting results may be explained by the fact that in the in silico analysis only the production of IL37 from PBMC was evaluated, whereas measurement of the circulating levels of IL37 also takes into account the production of IL37 from other non-immune sources including uterus and gastrointestinal cells for example [17]. Although our study is the first to demonstrate increased levels of IL37 during relapses of MS, two previous studies found augmented blood levels of IL37 in Iranian patients suffering from RR-MS and NMO.…”

“…IL37 is a cytokine belonging to the IL1 family that was originally discovered by in silico research [15]. IL37 can be found in the cytoplasm and nucleus [16] and is detectable in many human cells, including monocytes; natural killer (NK) cells; stimulated B cells; and tissues such as thymus, bone marrow, lymph nodes, colon, lung, and uterus [17]. The human IL37 gene is located on chromosome 2 and undergoes alternative splicing.…”

Epigenetic reprogramming in periodontal disease: Dynamic crosstalk with potential impact in oncogenesis

“…It has been discussed that such a biological function of interleukin-37 could be captured as a clinically successful therapeutic target for the treatment of periodontal inflammation and cancers. 92,93 To explore other similarities between shared epigenome alterations in both periodontitis and cancer, methylation-specific PCR for E-cadherin and cyclooxygenase-2 was performed. 94 while in the breast neoplastic tissue, the gene-silencing detection rate was 38% and 35%, respectively.…”