Interleukin-17 in rheumatoid arthritis: Trials and tribulations

Abstract

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine with well-characterized biological effects on stromal cell activation, angiogenesis, and osteoclastogenesis. The presence of this cytokine in the inflamed joints of patients with rheumatoid arthritis (RA), together with compelling data from in vitro and experimental arthritis models demonstrating its pro-inflammatory effects, made this cytokine a strong candidate for therapeutic targeting. Clinical trials, however, have shown relatively modest success in RA as compared with other indications. Guided by recent insights in IL-17 biology, this review aims to explore possible reasons for the limited clinical efficacy of IL-17A blockade in RA, and what we can learn from these results going forward.

The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

“…According to recent studies, the most of RA-promoting properties of IL-17 occurs from its synergistic effects with other cytokines (most importantly with TNF-α [ 105 ]) during the early stages of affliction establishment, forming self-perpetuating loops of pro-inflammatory activators and effectors [ 106 ]. IL-17 increases the production of IL-1β, IL-6, IL-8, IL-23, TNF-α, PGE2 and GM-CSF [ 99 , 100 , 101 , 105 , 107 ]. IL-17 also enhances those harmful interactions via recruitment and maintenance of inflammatory cells such as neutrophils, T cells or dendritic cells [ 101 ].…”

Traditional application and modern pharmacological research of Eucommia ulmoides Oliv.

“…In addition, it suppressed the proliferation of synoviocytes and prevented bone tissue damage which characterized by decreased RANKL mRNA whereas increased OPG mRNA expression [ 37 ]. The roles of Th17 cells and IL-17 in RA have been well reviewed recently [ 46 , 47 ]. Afterwards, conducted by the same team, ethanol extract of E. ulmoides cortex was fractionated with AcOEt and n-butyl alcohol sequentially, all fractions and extract (each dose of raw herbs at 4 g/kg) increased OPG/RANKL ratio, decreased MMP-9 expression, and inhibited IKK/NF-κB signaling pathway, whereas AcOEt fraction exhibited better improvement effect on OPG/RANKL system than others [ 35 ].…”

Cystic Fibrosis Lung Disease in the Aging Population

“…Anti-IL-17 antibodies have been shown to decrease neutrophil recruitment in murine airways when exposed to lipopolysaccharide (Ferretti et al, 2003). Anti-IL-17 has been tested clinically in rheumatoid arthritis and psoriasis (Ly et al, 2019;Taams, 2020) and might FIGURE 2 | CFTR modulator therapy in CF and potential effects on the hallmarks of aging. Color code for current level of evidence with blue no evidence for involvement in CF pathology, green weak evidence, yellow strong evidence.…”