Interleukin-12 regulates the response to chemotherapy in experimental visceral Leishmaniasis.

Abstract

In experimental visceral leishmaniasis, interleukin (IL)-12 initiates control over Leishmania donovani via Th1 cell activation, interferon (IFN)-gamma secretion, and granuloma formation. Because the leishmanicidal effect of conventional therapy, pentavalent antimony (Sb), also requires T cells and endogenous IFN-gamma, we tested IL-12 as a determinant of host responsiveness to chemotherapy. L. donovani-challenged IL-12p35 gene knockout (KO) mice permitted uncontrolled hepatic infection and failed to respond to Sb. In contrast, 96% of liver parasites in KO mice were killed by amphotericin B, which acts independently of immune responses. Exogenous IL-12 combined with Sb was tested in normal mice: low-dose Sb was converted from weakly to strongly leishmanicidal, and a no-effect Sb dose was converted to approximately 100% leishmanistatic. IL-12 plus Sb synergism in normal mice was IFN-gamma dependent; however, IL-12 also increased responsiveness to Sb in IFN-gamma KO mice. Thus, IL-12 regulates host IFN-gamma-dependent and -independent responses that permit and/or enhance the leishmanicidal activity of Sb.

• Authors: H W Murray, C Montelibano, R Peterson, J P Sypek
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 182 Issue 5 Pg. 1497-502 (Nov 2000) ISSN: 0022-1899 [Print] United States
• PMID: 11023473 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-12
• Interleukin-4
• Interferon-gamma
• Antimony

Topics

• Animals
• Antimony (therapeutic use)
• Interferon-gamma (physiology)
• Interleukin-12 (physiology)
• Interleukin-4 (physiology)
• Leishmaniasis, Visceral (drug therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout