Lactoferrin modulation of mycobacterial cord factor trehalose 6-6'-dimycolate induced granulomatous response.
The immune system responds to tuberculosis (TB) infection by forming granulomas. However, subsequent immune-mediated destruction of lung tissue is a cause of significant morbidity and contributes to disease transmission. Lactoferrin, an iron-binding glycoprotein, has demonstrated immunomodulatory properties that decrease tissue destruction and promote T(H)1 immune responses, both of which are essential for controlling TB infection. The cord factor trehalose 6,6'-dimycolate (TDM) model of granuloma formation mimics many aspects of TB infection with a similar histopathology accompanied by proinflammatory cytokine production. C57BL/6 mice were injected intravenously with TDM. A subset of mice was given 1 mg of bovine lactoferrin 24 h post-TDM challenge. Lung tissue was analyzed for histological response and for the production of proinflammatory mediators. C57BL/6 mice demonstrated a granuloma formation that correlated with an increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α,) IL-12p40, interferon-gamma (IFN-γ), and IL-10 protein. Mice treated with lactoferrin postchallenge had significantly fewer and smaller granulomas compared with those given TDM alone. Proinflammatory and T(H)1 cytokines essential to the control of mycobacterial infections, such as TNF-α and IFN-γ, were not significantly different in mice treated with lactoferrin. Furthermore, the anti-inflammatory cytokines IL-10 and transforming growth factor-β were increased. A potential mechanism for decreased tissue damage observed in the lactoferrin-treated mice is proposed. Because of its influence to modulate immune responses, lactoferrin may be a useful adjunct in the treatment of granulomatous inflammation occurring during mycobacterial infection.
Welsh
Kerry J
KJ
Medical School, Department of Pathology and Laboratory Medicine, University of Texas-Houston, Houston, Tex 77030, USA.
Hwang
Shen-An
SA
Hunter
Robert L
RL
Kruzel
Marian L
ML
Actor
Jeffrey K
JK
D000818:Animals; D003311:Cord Factors / Q000633:toxicity*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006099:Granuloma / Q000139:chemically induced* / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy / Q000517:prevention & control
D003311:Cord Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007781:Lactoferrin