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


Journal

International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259

Informations de publication

Date de publication:
Aug 2022
Historique:
received: 25 02 2022
revised: 29 04 2022
accepted: 02 05 2022
pubmed: 14 5 2022
medline: 22 6 2022
entrez: 13 5 2022
Statut: ppublish

Résumé

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. 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. 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]. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 35561480
pii: S1567-5769(22)00309-5
doi: 10.1016/j.intimp.2022.108825
pii:
doi:

Substances chimiques

Inflammasomes 0
Interleukin-1beta 0
NLR Family, Pyrin Domain-Containing 3 Protein 0
Caspase 1 EC 3.4.22.36
Zinc J41CSQ7QDS

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

108825

Informations de copyright

Copyright © 2022 Elsevier B.V. All rights reserved.

Auteurs

Amir Hossein Faghfouri (AH)

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Behzad Baradaran (B)

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Alireza Khabbazi (A)

Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Mahdi Abdoli Shadbad (M)

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Shahab Papi (S)

Department of Public Health, Faculty of Health, Social Determinants of Health Research Center, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.

Elnaz Faghfuri (E)

Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

Yaser Khajebishak (Y)

Department of Nutrition, Maragheh University of Medical Sciences, Maragheh, I.R., Iran.

Shima Rahmani (S)

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Parastoo Tolou Hayat (P)

Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Beitullah Alipour (B)

Department of Community Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: alipourb@tbzmed.ac.ir.

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Classifications MeSH