Researchers outline the significant role IL-37 plays in psoriasis, and other skin and connective tissue diseases, suggesting the need for further research, according to a review.
Researchers outline the significant role IL-37 plays in psoriasis, and other skin and connective tissue diseases, suggesting the need for further research, according to a review published in the journal Biomedicine and Pharmacotherapy.
“Over 40 years after ‘interleukin-1’ was termed, Interleukin-1 (IL-1) family has expanded to comprise 11 members, including the agonists IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β and IL-36γ, the antagonists IL-1Ra, IL-36Ra and IL-38, and the anti-inflammatory cytokine IL-37. They share a highly conserved β‐barrel structure, bind to extracellular immunoglobulin-like domains, and generally lack a signal peptide. IL-1 family plays a crucial role in immune homeostasis and contributes to various pathologies of autoimmunity and autoinflammation, dysmetabolism, cardiovascular diseases and neoplasms,” said the study authors.
The review explained that in psoriasis, inflammatory myeloid dendritic cells release IL-23 and IL-12 in order to activate Th1, Th17, and Th22 cells to produce cytokines IL-17, IFN-gamma, TNF, and IL-22. The researchers noted that keratinocytes (KC) are the main source of Il-17, while L-17, IFN-γ, IL-22, and TNF promote KC proliferation along with production of chemokine, cytokine and AMP.
For psoriasis, 3 previous studies revealed that IL-37 is downregulated in lesional skin compared to non-lesional skin in patients with psoriasis and healthy control skin from healthy individuals. Furthermore, RNA sequencing of 12 paired samples demonstrated that the expression of IL-37 in non-lesional skin was elevated versus healthy control skin; however, another study reported a higher expression of IL026 in psoriatic lesion compared with health controls.
“These contrary results possibly due to the experimental assays. As IL-37 consists of different isoforms and is rather low, which make it difficult to be detected by IHC or ELISA,” explained the study authors. “Biologic therapies have confirmed the efficacy of anti-IL-23, anti-TNF-α, and anti-IL-17 agents in ameliorating most clinical signs and symptoms in psoriasis patients. Worth mentioning, tofacitinib increased the expression of IL-37 in psoriasis patients rapidly.”
Additional studies showed that higher IL-37 serum levels are positively correlated with psoriasis disease severity during remission phase.
The study authors conclude that the overall findings emphasize the potential role of IL-37 as a therapeutic target in psoriasis and psoriatic arthritis. However, further research is necessary in order to explore IL-37 expression in the circulation, synovium, and skin lesion to determine clinical significance of IL-37 in psoriasis.
Pan Y, Wen X, Hao D, et al. The role of IL-37 in skin and connective tissue diseases [published online December 30, 2019]. Biomed Pharmacother. doi: 10.1016/j.biopha.2019.109705.