Lactoferrin as a Natural Immune Modulator Original paper

What was reviewed?

This review comprehensively examined lactoferrin, a multifunctional iron-binding glycoprotein, highlighting its capacity as a natural immunomodulator that bridges innate and adaptive immunity. The paper assessed lactoferrin’s roles in infection, inflammation, oxidative stress, and immune system regulation, including its therapeutic potential in systemic inflammatory response syndrome (SIRS), sepsis, and bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA).

Who was reviewed?

The review synthesized findings from preclinical in vivo and in vitro studies, particularly in murine models, along with limited human data, to explore the immune mechanisms regulated by lactoferrin. It included evidence across diverse immune cell types, including macrophages, neutrophils, dendritic cells, and T and B lymphocytes.

What were the most important findings?

Lactoferrin significantly modulates immune function through both direct and indirect pathways. It acts as an antimicrobial by binding iron, limiting pathogen proliferation, and neutralizing lipopolysaccharides (LPS). In the microbiome context, this review emphasizes that lactoferrin plays a regulatory role by reducing oxidative stress through iron sequestration and decreasing reactive oxygen species (ROS), which often rise during inflammatory and infectious states.

Lactoferrin dampens excessive immune responses during sepsis and endotoxemia by suppressing mitochondrial ROS and pro-inflammatory cytokines such as IL-6 and TNF-α. It also protects mucosal integrity by reducing bacterial translocation, especially in gut-associated lymphoid tissue. Notably, in both Gram-negative (E. coli) and Gram-positive (MRSA) infection models, lactoferrin improved survival and reduced inflammatory biomarkers. Regarding adaptive immunity, lactoferrin promotes Th1 responses, enhances antigen presentation via dendritic cells and macrophages, and drives T-cell maturation and B-cell isotype switching—thereby reinforcing host microbial surveillance and immunological memory.

Microbiome relevance lies in lactoferrin’s ability to preserve mucosal immunity, reduce gut inflammation, and prevent dysbiosis-linked bacterial dissemination, especially under systemic infectious stress. These actions suggest lactoferrin supports a microbiome-resilient host immune state.

What are the implications of this review?

This review highlights lactoferrin’s potential as a natural immunomodulatory intervention. Its ability to simultaneously enhance protective immunity while dampening harmful inflammation makes it a promising candidate for clinical use in sepsis, autoimmune diseases, infections, and potentially microbiome-targeted therapies. Its role in bridging innate and adaptive immunity also supports its use as a vaccine adjuvant, especially for pathogens requiring strong Th1-type responses. For microbiome-focused clinicians, lactoferrin’s action on mucosal immunity and bacterial translocation pathways suggests a powerful tool for managing dysbiosis-linked systemic inflammation.