Regulation of NLRP3 inflammasome by zinc supplementation in Behçet's disease patients: A double-blind, randomized placebo-controlled clinical trial

Abstract

Background: Overproduction of NLRP3 inflammasome complex is one of the causes of Behcet's disease's (BD) auto-inflammatory nature. The aim of current study was to examine the effect of zinc supplementation on NLRP3 inflammasome expression; as well as clinical manifestations of BD.

Methods: In this double-blind parallel placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day elemental zinc) or placebo groups for 12 weeks. The mRNA expression of NLRP3 and caspase-1 in the leukocytes, serum level of zinc and IL-1β, anthropometric measures, and clinical manifestations of patients were collected at pre- and post-intervention phase. The Iranian Behçet's disease dynamic activity measure (IBDDAM) was scored to measure the treatment effect using the calculation of number needed to treat (NNT). Analysis of covariance was performed to obtain the corresponding effect sizes.

Results: Zinc gluconate led to a significant improvement in genital ulcer (P = 0.019). Zinc supplementation decreased NLRP3 and caspase-1 genes expression compared with placebo group (baseline-adjusted P-value = 0.046 for NLRP3 and P-value = 0.003 for caspase-1), even after adjustment for the effect of confounding factors (baseline- and confounders-adjusted P-value = 0.032 for NLRP3 and P-value = 0.004 for caspase-1). Baseline and confounders adjusted effect size demonstrated that zinc was effective in reducing the serum level of IL-1β (P = 0.046). The NNT [95 %CI] for the rate of IBDDAM improvement was 3 [1.7-8.5].

Conclusions: Zinc gluconate supplementation (30 mg/day) for a 3-month period can be considered as an adjuvant therapy in alleviating inflammation and genital ulcer among BD patients.

Keywords: Behcet syndrome; Caspase 1; Interleukin-1beta; NLRP3; Zinc.