Cytokines in Systemic Lupus Erythematosus—Focus on TNF-α and IL-17

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder known for its complex pathogenesis, in which cytokines play an essential role. It seems that the modulation of these cytokines may impact disease progression, being considered potential biomarkers. Thus, TNF (tumor necrosis factor)-α and IL (interleukin)-17 are molecules of great interest in SLE. TNF-α plays a dual role in SLE, with both immunosuppressive and proinflammatory functions. The role of IL-17 is clearly described in the pathogenesis of SLE, having a close association with IL-23 in stimulating the inflammatory response and consecutive tissue destruction. It appears that patients with elevated levels of these cytokines are associated with high disease activity expressed by the SLE disease activity index (SLEDAI) score, although some studies do not confirm this association. However, TNF-α and IL-17 are found in increased titers in lupus patients compared to the general population. Whether inhibition of these cytokines would lead to effective treatment is under discussion. In the case of anti-TNF-α therapies in SLE, the possibility of ATIL (anti-TNF-induced lupus) is a serious concern that limits their use. The use of anti-IL-17 therapies in SLE is a promising option, but not yet approved. Future studies of these cytokines in large cohorts will provide valuable information for the management of SLE.

Imbalance of Th17 cells, Treg cells and associated cytokines in patients with systemic lupus erythematosus: a meta-analysis

“…Regarding IL-21, it is not only expressed by Th17 cells but also involved in the initiation phase of Th17 cell differentiation ( 63 ). Notably, IL-21 cooperates with IL-17 to stimulate an inflammatory response and generates tissue damage in SLE ( 64 ). In the meanwhile, IL-6 is known to drive the expansion of Th17 cells, suggesting that the IL-17/IL-6 axis induces a positive feedback loop in SLE ( 65 ).…”

Biomarkers in Systemic Lupus Erythematosus along with Metabolic Syndrome

“…For instance, tumor necrosis factor-alpha (TNF-α) is considered a central proinflammatory cytokine studied in IR that modulates the activity and expression of enzymes blocking insulin function [25]. High levels of TNF-α have been found in SLE patients with active lupus, demonstrating the enhanced risk of IR in these patients [26].…”

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF

“…It plays an important role in the regulation of the immune response through the induction of a pro-inflammatory response to pathological infections [4,5]. The main source of soluble TNF is monocytic cells, but they are known for being secreted by lymphocytes [6]. TNF, in the acute phase of infection, affects intercellular contacts and adhesion molecules, making it easier for cells of the immune system to access the site of infection from the circulatory system.…”