Atefeh Alaei1,2,3, Mahmoud Mahmoudi1,2, Maryam Sahebari4, Zohreh Vahidi5, Nafiseh Tabasi1, Maryam Rastin1,2*

1Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
4Rheumatic Disease Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
5Division of Inflammation and Inflammatory Diseases, Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Keywords: Cytokines, immunomodulatory, Lactobacillus delbrueckii, Lactobacillus rhamnosus, systemic lupus erythematosus.


Objectives: This study aimed to assess the ex vivo impact of Lactobacillus delbrueckii (L. delbrueckii) and Lactobacillus rhamnosus (L. rhamnosus) on inflammatory and anti-inflammatory cytokines as well as their related molecules on the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients.

Patients and methods: This study was conducted with 20 newly diagnosed SLE patients (18 females, 2 males; mean age: 33.3±12.4 years; range, 18 to 68 years) between September 2017 and September 2018. Extracted PBMCs from each patient were divided into 4 cell groups in our study. Three cell groups act as treatment groups receiving L. rhamnosus (107 CFU/mL), L. delbrueckii (105 CFU/mL) or a mixture of both, and one group act as our untreated control group in the absence of any probiotic agents. All cell groups were cultured in RPMI 1460 medium for 48 h. Then, total RNA was extracted, and cDNA was synthesized.

Results: The gene expression levels of forkhead box P3 (FOXP3), transforming growth factor beta (TGF-β), interleukin (IL)-6, IL-10, and IL-2 were evaluated by a quantitative real-time polymerase chain reaction. The results revealed that expression levels of FOXP3, TGF-β, IL-10, and IL-2 increased and the level of IL-6 decreased in probiotics-receiving groups compared to the control group. Lactobacillus delbrueckii and L. rhamnosus enhanced the expression of regulatory T cell-related molecules such as FOXP3 and IL-2 and also increased the expression of IL-10. These probiotics also reduced the expression of IL-6 as proinflammatory cytokines in the PBMCs of SLE patients.

Conclusion: The results of the present study show that these probiotics could be effective in regulating the balance of cytokine gene expression ex vivo , and due to their beneficial effects, they can be an intriguing option in the production of new complement drugs for SLE

Citation: Alaei A, Mahmoudi M, Sahebari M, Vahidi Z, Tabasi N, Rastin M. The effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on cytokines and their related molecules: An ex vivo study on patients with systemic lupus erythematosus. Arch Rheumatol 2023;38(4):642-652. doi: 10.46497/ ArchRheumatol.2023.9941

Ethics Committee Approval

The study protocol was approved by the Mashhad University of Medical Sciences Ethics Committee (date: 14.06.2017, no: The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Idea/concept, design: M.R., M.M.; Control/supervision, references and fundings, materials: M.R.; Data collection and/or processing: A.A., M.S., N.T., Z.V.; Analysis and/or interpretation: M.M.; Literature review: A.A., M.R.; Writing the article: A.A.; Critical review: M.R., M.M.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This work was supported by Mashhad University of Medical Sciences (MUMS) under Grant number 951444.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.