Randomized double-blinded controlled trial on the effect of synbiotic supplementation on IL-17/IL-23 pathway and disease activity in patients with axial spondyloarthritis.

BACKGROUND: Interleukin 17 (IL17)-expressing CD4+ T cells and IL-17/IL-23 pathway play a key role in the pathogenesis of axial spondyloarthritis (axSpA). Synbiotics have been suggested due to their immunomodulatory effects in the treatment of autoimmune diseases. This randomized double-blind, placebo-controlled trial was designed to assess the effects of synbiotic supplement on IL-17/IL-23 pathway and disease activity in patients with axSpA. METHODS: Forty-eight axSpA patients were randomly allocated to use one synbiotic capsule or placebo daily for 12 weeks. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASAS-endorsed disease activity score-C-reactive protein (ASDAS-CRP). The secondary outcome was proportion of IL17-expressing CD4+ T cells, IL-17 and IL-23 gene expression, and supernatant levels of IL-17 and IL-23, which were measured at the baseline and end of the trial. RESULTS: A total of 48 patients were randomized into the synbiotic and placebo groups. Thirty-eight patients completed the study. Synbiotic supplementation significantly reduced the proportion of IL17-expressing CD4+ T cells (4.88 ± 2.47 vs. 2.16 ± 1.25), gene expression of IL-17 (1.03 ± 0.24 vs. 0.65 ± 0.26) and IL-23 (1.01 ± 0.13 vs. 0.68 ± 0.24) and serum IL-17 (38.22 ± 14.40 vs. 24.38 ± 11.68) and IL-23 (51.77 ± 17.40 vs. 32.16 ± 12.46) compared with baseline. Significant differences between groups were noticed only in the proportion of IL17-expressing CD4+ T cells, and IL-17 and IL-23 gene expression. Synbiotic supplementation did not significantly alter BASDAI and ASDAS-CRP compared with baseline and placebo group at the end of trial. CONCLUSION: Present study indicated beneficial effect of synbiotic supplement on IL-17/IL-23 pathway without improving disease activity in axSpApatients.HighlightsSynbiotic supplementation reduced IL17-expressing CD4+ T cells proportion in axSpA.Synbiotic supplementation decreased IL-17 and IL-23 gene expression in axSpA.Synbiotic supplementation did not change disease activity score in axSpA.

Effects of synbiotic supplementation on regulatory T cells' response in patients with axial spondyloarthritis: a randomized double-masked placebo-controlled trial.

This study was conducted on samples from patients enrolled in a randomized double-masked placebo-controlled trial on the effect of synbiotic supplementation on the IL-17/IL-23 pathway and disease activity in patients with axial spondyloarthritis (axSpA) to investigate the effects of synbiotic supplementation on regulatory T (Treg) cells' response in these patients. Forty-eight axSpA patients were randomized to take one synbiotic capsule or placebo daily for 12 weeks. Treg cell proportion, gene expression of forkhead box protein P3 (Foxp3), microRNA (miRNA)-25, miRNA-106b, miRNA-146a, interleukin (IL)-10, and transforming growth factor (TGF)-ß as well as serum IL-10 and TGF-ß levels were assessed before and after the trial. Thirty-eight patients (19 in each group) completed the trial. The proportion of Treg cells (P < 0.001), the gene expression of FoxP3 (P < 0.001), IL-10 (P = 0.001), TGF-ß (P < 0.001), and miRNA-146a (P < 0.001) and serum IL-10 (P = 0.003) and TGF-ß (P = 0.002) levels significantly increased compared to the baseline in the synbiotic group. Additionally, a significant reduction in the gene expression of miRNA-25 (P < 0.001) and miRNA-106b (P < 0.001) was observed in the synbiotic group. Significant between-group differences were observed in the proportion of Treg cells (P = 0.024) and the gene expression of FoxP3 (P = 0.010), IL-10 (P = 0.002), TGF-ß (P = 0.016), miRNA-25 (P = 0.008), miRNA-106b (P = 0.001), and miRNA-146a (P = 0.010). Differences in the serum levels of IL-10 and TGF-ß between the groups were not significant. As a conclusion, synbiotic supplementation could modulate Treg cells' response in axSpA patients and thus can be promising as an adjunctive therapy. Additional investigations would help in further clarifying the subject.

Comparison of losartan and amlodipine effects on the outcomes of patient with COVID-19 and primary hypertension: A randomised clinical trial.

BACKGROUND: Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID-19. METHODS: In this randomised clinical trial, hospitalised patients with COVID-19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30-day mortality rate and length of hospital stay. RESULTS: The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30-day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). CONCLUSIONS: There was no priority in losartan or amlodipine administration in COVID-19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first-line anti-HTN medications in COVID-19.