Lactoferrin modulation of IL-12 and IL-10 response from activated murine leukocytes
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Lactoferrin possesses a wide range of immunomodulatory activities, including promotion of the delayed type hypersensitivity response (DTH) towards BCG (Bacillus Calmette Guerin) antigens. Addition of Lactoferrin as an adjuvant to the BCG vaccine was previously demonstrated to augment protection against subsequent mycobacterial challenge, with concomitant development of a strong T cell helper type 1 (TH1) immunity. Because generation of TH1 immunity is in large part dependent on the balance of monocytic pro- and anti-inflammatory cytokines, the effect of Lactoferrin on leukocytes was investigated. Lactoferrin enhanced proinflammatory responses in a dose-dependant manner from splenocyte and adherent (F4/80+) splenocyte populations, bone marrow derived monocytes (BMM), and J774A.1 cultured cells. In all scenarios tested, Lactoferrin induced a strong increase in the ratio of IL-12:IL-10 production from LPS stimulated cells. Examination of Lactoferrin effects on BCG infected J774A.1 cells and on BMM revealed similar immunomodulatory effects, with particularly strong increase in IL-12 production. Furthermore, immunization of mice with BCG admixed with Lactoferrin led to increased generation of CD4+ cells expressing IFN-γ upon restimulation with BCG antigens. These results provide molecular evidence to support the role of Lactoferrin as an adjuvant candidate to augment development of DTH response to vaccine antigens.
KeywordsLactoferrin Macrophage IL-12 Vaccine adjuvant
This work was accomplished with support from NIH grant R41AI51050-01 and R42-AI051050-02. We thank Michal Zimecki Ph.D. (Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland) and Robert L. Hunter, M.D., Ph.D. (University of Texas-Houston Medical School, Department of Pathology) for helpful conversations and data discussion, and Margaret Olsen for assistance and technical expertise.
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