Immunomodulatory Effect of Bovine Lactoferrin During SARS-CoV-2 Infection

Introduction: Lactoferrin (Lf) is an important immunomodulator in infections caused by different agents. During SARS-CoV-2 infection, Lf can hinder or prevent virus access to the intracellular environment. Severe cases of COVID-19 are related to increased production of cytokines, accompanied by a weak type 1 interferon response.

Methods: We investigated the influence of bovine Lf (bLf) in the immune response during SARS-CoV-2 infection and assays.

Results: Our results show a strong binding between bLf and TLR4/NF-κB , as well as an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMCs) treated with bLf. Furthermore, the treatment increased mRNA expression in infected K18-hACE2 mouse blood, indicating an activation of innate response. Our results show that, when bLf was added, a reduction in the NK cell population was found, presenting a similar effect on PD-1 in TCD4 and TCD8 cells. In the culture supernatant of PBMCs from healthy participants, bLf decreased IL-6 levels and increased CCL5 in COVID-19 participants. In addition, K18-hACE2 mice infected and treated with bLf presented an increase of serum pro-inflammatory markers (GM-CSF/IL-1β/IL-2) and upregulated mRNA expression of and in the lung tissue. Furthermore, bLf treatment was able to restore levels in brain tissue.

Discussion: The data indicate that bLf can be part of a therapeutic strategy to promote the immunomodulation effect, leading to homeostasis during COVID-19.

Citing Articles

Lactoferrin: Properties and Potential Uses in the Food Industry.

Demir R, Saritas S, Bechelany M, Karav S Int J Mol Sci. 2025; 26(4).

PMID: 40003872 PMC: 11855648. DOI: 10.3390/ijms26041404.

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