The immunomodulatory effects of lactoferrin and its derived peptides on NF‐κB signaling pathway: A systematic review and meta‐analysis

Abstract

BackgroundLactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS, thereby intervening in certain signaling pathways and biological processes. In the present meta‐analysis, we aimed to pool experimental data regarding the immunomodulatory effects of lactoferrin and its derived peptides on the NF‐κB signaling pathway.MaterialsWe searched PubMed, Google Scholar, and Web of Science databases and obtained all related articles published before April 2022. Finally, 25 eligible studies were selected, and their reports were analyzed.MethodsWe used Review Manager Version 5.2 to compute the standardized mean difference (SMD) and its 95% confidence interval. In addition, the source of heterogeneity was explored using meta‐regression and sensitivity analysis. The symmetry of the funnel plot and Egger's test were also used to evaluate publication bias utilizing Comprehensive Meta‐Analysis Version 2.ResultsComparing the group of cells and animals exposed to lipopolysaccharide alone with the group that received pretreatment with lactoferrin and its derivatives, we observed significant reductions in TNF‐α, IL‐1 beta, and IL‐6 levels by 8.73 pg/mL, 2.21 pg/mL, and 3.24 pg/mL, respectively, in the second group. Additionally, IKK‐β, p‐IκB, and NF‐κB (p65) levels were significantly lower by 7.37‐fold, 15.02‐fold, and 3.88‐fold, respectively, in various cells and tissues.ConclusionBased on the results of this meta‐analysis, lactoferrin and its derived peptides can be considered potent prophylactic and therapeutic candidates against inflammation‐associated diseases by targeting the NF‐kB pathway.

Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products

“…Conversely, it has been reported that human transferrin and LF could modulate expression of streptococcal pyrogenic exotoxins (Spes) [ 117 ]. Down-regulation of SpeB may favor bacterial growth, preserving the integrity of M proteins and superantigens [ 118 , 119 ].…”

“…In the light of these findings, bLF may rep a potential therapeutic tool to protect the host during the toxic shock synd Conversely, it has been reported that human transferrin and LF could mo expression of streptococcal pyrogenic exotoxins (Spes) [117]. Down-regulation of may favor bacterial growth, preserving the integrity of M proteins and superan [118,119].…”

Neutrophil Extracellular Traps in Cardiovascular and Aortic Disease: A Narrative Review on Molecular Mechanisms and Therapeutic Targeting

“…Other proteases such as cathepsin G also aid in the neutralization of microbial components, breakdown of extracellular matrix (ECM) proteins, and recruitment of immune cells to the site of infection/inflammation [26]. NETs may also contain other types of molecules, such as lactoferrin and pentraxins, which additionally modulate the immune response [27,28]. Thus, the local accumulation and coordinated response of various neutrophil granule components contribute to the effectiveness of NETs in host defense [29].…”