IL4-10 synerkine induces direct and indirect structural cartilage repair in osteoarthritis

Abstract

p ¼< 0.000 and p ¼< 0.000 and in total WOMAC score, p ¼< 0.000 and p ¼< 0.000) over TA group. Primary efficacy end point outcome (improvement ! 40%) of total WOMAC scores at 12 weeks, in Hylan G-F 20 and TA groups respectively was 30 (66.7%) and 5 (13.2%) in target knee joints (p ¼< 0.00) and at 26 weeks 35 (77.8%) and 10 (26.3%) in target knee joints (p ¼< 0.001). Within the group, VAS for pain reduction reported by patients and the investigator were significant statistically both at 12 and 26 weeks and in between groups, at weeks 12 (patient, p ¼ 0.002; investigator, p ¼ 0.001) and at weeks 26 (patient, p ¼ 0.000; investigator, p ¼ 0.000) respectively. Joint space improvement was also significant both at12 weeks (p ¼ 0.044) and 26 weeks (p ¼ 0.003) for Hylan G-F 20 than TA. Conclusions: A significant pain reduction, improvement in joint rheology and quality of life was observed with use of high molecular weight visco-supplementation (Hylan G-F 20) in patients suffering from primary knee OA refractory to standard care. Besides comparable efficacy both agents were found safe. Large scale project with longer follow up might answer long term outcomes.

Joint Dysfunctionality Alleviation along with Systemic Inflammation Reduction Following Arthrocen Treatment in Patients with Knee Osteoarthritis: A Randomized Double-Blind Placebo-Controlled Clinical Trial

“…Since these two cytokines inhibit the joint production of destructive enzymes (e.g., metalloproteinase), they can prevent the destruction of cartilage and its surrounding tissue [32][33][34][35][36]. In practice, it has also been proven that IL4-10 boosts direct and indirect structural cartilage repair in osteoarthritis [37].…”

Interleukin-36γ–producing macrophages drive IL-17–mediated fibrosis

“…The macrophages associated with UBM and IL-4 in the tissue are heterogeneous and distributed in phenotypically distinct clusters. IL-4 is a cytokine recognized for promoting repair of muscle (9), liver (29), and cartilage (30) and is critical for macrophage polarization in a healing wound (31). The UBM environment induced greater macrophage heterogeneity with two primary terminal subsets with phenotypes relevant to tissue repair.…”

Synovitis in osteoarthritis: current understanding with therapeutic implications

“…Although the literature is limited, there is emerging evidence that an up-regulation of these cytokines, either individually or combined, may induce cartilage repair in OA. A novel fusion protein of IL-4 and IL-10 has induced both structural repair and reduced inflammation ex vivo, and inhibited pain in animal models of OA [ 18 ].…”