Affiliation:
1. Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021
2. Center for Global Health and Disease, Case Western University School of Medicine, Cleveland, Ohio 44106
Abstract
ABSTRACT
To determine if stimulation of Th1-cell-associated immune responses, mediated by interleukin 12 (IL-12) and gamma interferon (IFN-γ), enhance the antileishmanial effect of amphotericin B (AMB),
Leishmania donovani
-infected BALB/c mice were first treated with (i) exogenous IL-12 to induce IFN-γ, (ii) agonist anti-CD40 monoclonal antibody (MAb) to maintain IL-12 and induce IFN-γ, or (iii) anti-IL-10 receptor (IL-10R) MAb to blockade suppression of IL-12 and IFN-γ. In animals with established visceral infection, low-dose AMB alone (two injections of 1 mg/kg of body weight; total dose, 2 mg/kg) killed 15 to 29% of liver parasites; by themselves, the immunointerventions induced 16 to 33% killing. When the interventions were combined, the leishmanicidal activities increased 3.4-fold (anti-CD40), 6.3-fold (anti-IL-10R), and 9-fold (IL-12) compared with the activities of AMB plus the control preparations; and overall killing (76 to 84%) approximated the 84 to 92% killing effect of 7.5-fold more AMB alone (three injections of 5 mg/kg; total dose, 15 mg/kg). These results suggest that strengthening the host Th1-cell response may be a strategy for the development of AMB-sparing regimens in visceral leishmaniasis.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference41 articles.
1. Balkhy, H. H., and F. P. Heinzel. 1999. Endotoxin fails to induce interferon-γ in endotoxin tolerant mice: deficiencies in both IL-12 heterodimer production and IL-12 responsiveness. J. Immunol.162:3633-3638.
2. Bennett J. E. 2001. Amphotericin B p. 1295-1299. In J. C. Hardman and L. E. Limbird (ed.) Goodman & Gilman's the pharmacological basis of therapeutics 10th ed. McGraw-Hill New York N.Y.
3. Berman, J. D., and D. J. Wyler. 1980. An in vitro model for chemotherapeutic agents in leishmaniasis. J. Infect. Dis.142:83-86.
4. Immunoadjuvant activity of amphotericin B as displayed in mice infected with Candida albicans
5. Blanke, T. J., J. R. Little, S. F. Shirley, and R. G. Lynch. 1977. Augmentation of murine immune responses by amphotericin B. Cell. Immunol.33:180-190.
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