Immunomodulatory effects of recombinant lactoferrin during MRSA infection.

International immunopharmacology

PubMedID: 24613206

Hwang SA, Kruzel ML, Actor JK. Immunomodulatory effects of recombinant lactoferrin during MRSA infection. Int Immunopharmacol. 2014;.
Methicillin-resistant Staphylococcus aureus (MRSA) infection remains a serious hazard to global health despite increases in public education and development of innovative treatment strategies. Use of immune modulatory therapy to combat infection is gaining interest as a novel treatment alternative. Lactoferrin (LF), an iron binding protein with multiple immune modulating properties, has the potential to modify the course of systemic MRSA infection. Specifically, LF is capable of limiting deleterious inflammatory responses while promoting development of antigen specific T-cell activity. The efficacy of a novel recombinant mouse LF (rmLF) to protect against MRSA infection was examined in a mouse peritonitis model. BALB/c mice were infected with a lethal dose of MRSA and treated at 2h post-infection with rmLF. The effects of rmLF on MRSA-infected primary monocytes and granulocytes were analyzed for inflammatory mediator production. The rmLF treated mice demonstrated only modest increase in survival by more than 24h, albeit with reduced bacteremia. Serum cytokines, IL-17 and IL-6, were significantly reduced post-challenge in the rmLF treated mice. Treatment with rmLF led to a minor decrease in IL-1ß, and a slight increase in TNF-a production. Preliminary investigation towards human clinical relevance was accomplished using human blood derived monocytes and granulocytes infected with MRSA and treated with a homologous recombinant human LF (rhLF). Treatment with (rhLF) led to an increased production of IFN-? and IL-2. The human cell studies also showed a concurrent decrease in TNF-a, IL-6, IL-1ß, IL-12p40, and IL-10. The study reports the first investigation into the efficacy of a novel recombinant mouse lactoferrin (LF) therapy in a mouse model of MRSA peritonitis. Overall, these results indicate that the rmLF and rhLF have a high degree of overlap to modify inflammatory responses, although differences in activities were observed indicating the existence of mechanisms between the two heterologous recombinant molecules.