Recombinant Human Lactoferrin Reduces Inflammation and Increases Fluoroquinolone Penetration to Primary Granulomas During Mycobacterial Infection of C57Bl/6 Mice

Abstract

Infection with Mycobacterium tuberculosis ( Mtb ) results in the primary formation of a densely packed inflammatory foci that limits entry of therapeutic agents into pulmonary sites where organisms reside. No current therapeutic regimens exist that modulate host immune responses to permit increased drug penetration to regions of pathological damage during tuberculosis disease. Lactoferrin is a natural iron-binding protein previously demonstrated to modulate inflammation and granuloma cohesiveness, while maintaining control of pathogenic burden. Studies were designed to examine recombinant human lactoferrin (rHLF) to modulate histological progression of Mtb -induced pathology in a non-necrotic model using C57Bl/6 mice. The rHLF was oral administered at times corresponding to initiation of primary granulomatous response, or during granuloma maintenance. Treatment with rHLF demonstrated significant reduction in size of primary inflammatory foci following Mtb challenge, and permitted penetration of ofloxacin fluoroquinolone therapeutic to sites of pathological disruption where activated (foamy) macrophages reside. Increased drug penetration was accompanied by retention of endothelial cell integrity. Immunohistochemistry revealed altered patterns of M1-like and M2-like phenotypic cell localization post infectious challenge, with increased presence of M2-like markers found evenly distributed throughout regions of pulmonary inflammatory foci in rHLF treated mice.

Colostrum and Lactoferrin Protect against Side Effects of Therapy with Antibiotics, Anti-inflammatory Drugs and Steroids, and Psychophysical Stress: A Comprehensive Review

“…In a mouse model, inflammatory foci in lungs of Mycobacterium tuberculosis -infected animals hamper the penetration of therapeutics to infected sites and bacteria destruction. Oral recombinant human LF (rhLF) was used in C57BL mice as an adjuvant therapy with ofloxacin fluoroquinolone [ 91 ]. Histological analysis revealed that treatment with LF enabled penetration of the antibiotic to the pathologic sites populated with activated macrophages.…”

Antibacterial properties of lactoferrin: A bibliometric analysis from 2000 to early 2022

“…Therefore, inhibiting the cytokine storm may be a prophylactic and therapeutic approach toward combating COVID-19 infection (Zimecki et al, 2021).In the study of pulmonary acute respiratory distress syndrome (ARDS) in granulomatous inflammation model (Mrityunjaya et al, 2020), it was found that LF can reduce or eliminate cytokine excess and pulmonary pathological features caused by Mycobacterium tuberculosis (Welsh et al, 2011;Hwang et al, 2017). In addition, LF was also able to diminish hyperacute immunopathology developed after the administration of isolated surface mycolic acid components (Nguyen et al, 2021(Nguyen et al, , 2022. LF significantly induced the expression of the antiviral immune response genes and partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells to protect against SARS-CoV-2 infection in vitro (Salaris et al, 2021).…”