Document 0016
 DOCN  M95B0016
 TI    Activity of pentostam (sodium stibogluconate) against cutaneous
       leishmaniasis in mice treated with neutralizing anti-interferon-gamma
       antibody.
 DT    9511
 AU    Nabors GS; Farrell JP; Department of Pathobiology, School of Veterinary
       Medicine,; University of Pennsylvania, Philadelphia, USA.
 SO    Am J Trop Med Hyg. 1995 Jul;53(1):55-60. Unique Identifier : AIDSLINE
       MED/95351471
 AB    Studies with Leishmania donovani in the mouse have demonstrated that an
       intact T cell compartment is required for effective anti-leishmanial
       therapy using pentavalent antimony compounds such as Pentostam (sodium
       stibogluconate), suggesting that the in vivo efficacy of drug treatment
       is at least partially immune-based. Similarly, Leishmania-infected,
       immunodeficient human patients including those with acquired
       immunodeficiency syndrome (AIDS) generally relapse following therapy
       with antimonials. However, sodium stibogluconate is directly
       parasiticidal in vitro, in the absence of T cells or T cell products.
       Using a model of a cutaneous form of leishmaniasis, in which susceptible
       BALB/c mice were infected with Leishmania major, we investigated whether
       the antileishmanial activity of the drug demonstrated a requirement for
       interferon-gamma (IFN-gamma), a cytokine produced during a T helper cell
       type 1 (Th1) immune response and known to contribute to resistance to
       infection, and whether drug therapy affected the nature of the
       antileishmanial response. Lesion development was suppressed in mice
       treated from the onset of infection with sodium stibogluconate alone,
       and in animals treated with sodium stibogluconate plus a neutralizing
       anti-IFN-gamma antibody, and tissue parasite burdens were approximately
       10,000-fold less at the end of therapy in both groups compared with
       controls. Lesion development was similarly suppressed in mice with
       established lesions treated with either sodium stibogluconate alone, or
       sodium stibogluconate plus anti-IFN-gamma antibody. The production of
       IFN-gamma by cells from infected animals was somewhat increased
       immediately following therapy with sodium stibogluconate, an effect that
       was not long-lasting, while interleukin-4 (IL-4) production was not
       affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Animal  Antibodies, Monoclonal/*THERAPEUTIC USE  Antimony Sodium
       Gluconate/ADMINISTRATION & DOSAGE/*PHARMACOLOGY/  THERAPEUTIC USE
       Cytokines/BIOSYNTHESIS  IgE/BIOSYNTHESIS  Injections, Intramuscular
       Interferon Type II/*IMMUNOLOGY  Leishmania major/*DRUG EFFECTS
       Leishmaniasis, Cutaneous/*DRUG THERAPY/IMMUNOLOGY  Mice  Mice, Inbred
       BALB C  Mice, Inbred C3H  Mice, Inbred C57BL  Support, U.S. Gov't,
       P.H.S.  Th1 Cells/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).