IL-1 Family Members in Cancer; Two Sides to Every Story

Abstract

The IL-1 family of cytokines currently comprises of seven ligands with pro-inflammatory activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) as well as two ligands with anti-inflammatory activity (IL-37, IL-38). These cytokines are known to play a key role in modulating both the innate and adaptive immunes response, with dysregulation linked to a variety of autoimmune and inflammatory diseases. Given the increasing appreciation of the link between inflammation and cancer, the role of several members of this family in the pathogenesis of cancer has been extensively investigated. In this review, we highlight both the pro- and anti-tumorigenic effects identified for almost all members of this family, and explore potential underlying mechanisms accounting for these divergent effects. Such dual functions need to be carefully assessed when developing therapeutic intervention strategies targeting these cytokines in cancer.

Long noncoding RNA BHLHE40‐AS1 promotes early breast cancer progression through modulating IL‐6/STAT3 signaling

“…The data presented here demonstrate that BHLHE40‐AS1 modulates a proinflammatory cytokine signature and is an important mediator of IL‐6/STAT3 signaling. IL‐1α and IL‐1β are pleiotropic activator cytokines that function as critical signaling mediators of the inflammatory tumor microenvironment . IL‐1β in particular is found to be upregulated in many cancers including breast cancer, and to support angiogenesis, proliferation, metastasis, and inflammasome activation at both primary and metastatic sites .…”

“…IL‐1α and IL‐1β are pleiotropic activator cytokines that function as critical signaling mediators of the inflammatory tumor microenvironment . IL‐1β in particular is found to be upregulated in many cancers including breast cancer, and to support angiogenesis, proliferation, metastasis, and inflammasome activation at both primary and metastatic sites . In breast cancer, IL‐1β expression induces IL‐6 and additional cytokines and growth factors .…”

Identification of hub genes in papillary thyroid carcinoma: robust rank aggregation and weighted gene co-expression network analysis

“…Signal transduction is very important in the occurrence of tumor [42]. Interleukin-1 plays a role in regulating innate immunity and adaptive immunity [43]. In particular, interleukin-1 has dual roles of anti-tumor and pro-tumor [43].…”

“…Interleukin-1 plays a role in regulating innate immunity and adaptive immunity [43]. In particular, interleukin-1 has dual roles of anti-tumor and pro-tumor [43]. Positive regulation of MAP kinase activity and metalloendopeptidase activity are thought to be associated with thyroid cancer [44,45].…”

Interleukin (IL)-1 family cytokine in primary immune thrombocytopenia: a comparison with systemic lupus erythematosus-associated thrombocytopenia

“…The family of interleukin 1 (IL-1) cytokines consists of 11 members, including 7 pro-inflammatory agonist, IL-1α (IL-1F1), IL-1β (IL-1F2), IL-18 (IL-1F4), IL-33 (IL-1F11), IL-36α (IL-1F6), IL-36β (IL-1F8) and IL-36γ (IL-1F9), initiating the proinflammatory signal and 4 antagonists or anti-inflammatory activity, IL-1 receptor antagonist (IL-1Ra, IL-1F3), IL-36Ra (IL-1F5), IL-37 (IL-1F7) and IL-38 (IL-1F10), inhibiting inflammation or trigger anti-inflammatory reactions [10]. IL-1 cytokine family is a family of protein molecules that play a crucial role as a major proinflammatory and immunoregulatory mediator in a wide range of autoinflammatory, infectious, tumor and autoimmune disease which act through receptors of the Toll-like/IL-1 receptor superfamily [11][12][13][14][15]. The productions of inflammatory cytokines such as IL-1, IL-36 and IL-18 activate target cells through the receptors superfamily then amplify the immune response.…”