Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute toxoplasmosis

被引:6
作者
Araujo, FG [1 ]
Hunter, CA [1 ]
Remington, JS [1 ]
机构
[1] STANFORD UNIV,SCH MED,STANFORD,CA 94305
关键词
D O I
10.1128/AAC.41.1.188
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of murine toxoplasmosis was examined, IL-12 (100 ng/injection), atovaquone (10 mg/kg of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused delayed time to death or minimal survival rates, In contrast, significant survival rates resulted when the same dose of lL-12 was used in combination with the same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated with IL-12 plus drug produced significantly higher levels of gamma interferon than controls, Although IL-12 was effective only when administered before infection, these results suggest that this cytokine may be a useful adjunct in the therapy of human toxoplasmosis in situations when cysts reactivate and tachyzoites start multiplying in immunocompromised patients.
引用
收藏
页码:188 / 190
页数:3
相关论文
共 17 条
[1]   STRATEGIES OF ANTICYTOKINE MONOCLONAL-ANTIBODY DEVELOPMENT - IMMUNOASSAY OF IL-10 AND IL-5 IN CLINICAL-SAMPLES [J].
ABRAMS, JS ;
RONCAROLO, MG ;
YSSEL, H ;
ANDERSSON, U ;
GLEICH, GJ ;
SILVER, JE .
IMMUNOLOGICAL REVIEWS, 1992, 127 :5-24
[2]   RIFABUTIN IS ACTIVE IN MURINE MODELS OF TOXOPLASMOSIS [J].
ARAUJO, FG ;
SLIFER, T ;
REMINGTON, JS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (03) :570-575
[3]   REMARKABLE INVITRO AND INVIVO ACTIVITIES OF THE HYDROXYNAPHTHOQUINONE 566C80 AGAINST TACHYZOITES AND TISSUE CYSTS OF TOXOPLASMA-GONDII [J].
ARAUJO, FG ;
HUSKINSON, J ;
REMINGTON, JS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (02) :293-299
[4]   SYNERGISTIC ACTIVITY OF AZITHROMYCIN AND GAMMA INTERFERON IN MURINE TOXOPLASMOSIS [J].
ARAUJO, FG ;
REMINGTON, JS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (08) :1672-1673
[5]   EFFECT OF CLINDAMYCIN ON ACUTE AND CHRONIC TOXOPLASMOSIS IN MICE [J].
ARAUJO, FG ;
REMINGTO.JS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1974, 5 (06) :647-651
[6]  
BEAMAN MH, 1995, PRINCIPLES PRACTICE, P2455
[7]   MITOGEN-SPECIFIC AND ANTIGEN-SPECIFIC PROLIFERATION OF T-CELLS IN MURINE TOXOPLASMOSIS IS INHIBITED BY REACTIVE NITROGEN INTERMEDIATES [J].
CANDOLFI, E ;
HUNTER, CA ;
REMINGTON, JS .
INFECTION AND IMMUNITY, 1994, 62 (05) :1995-2001
[8]   INTERLEUKIN-12 IS REQUIRED FOR THE T-LYMPHOCYTE-INDEPENDENT INDUCTION OF INTERFERON-GAMMA BY AN INTRACELLULAR PARASITE AND INDUCES RESISTANCE IN T-CELL-DEFICIENT HOSTS [J].
GAZZINELLI, RT ;
HIENY, S ;
WYNN, TA ;
WOLF, S ;
SHER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :6115-6119
[9]   DEVELOPMENT OF TH1 CD4+ T-CELLS THROUGH IL-12 PRODUCED BY LISTERIA-INDUCED MACROPHAGES [J].
HSIEH, CS ;
MACATONIA, SE ;
TRIPP, CS ;
WOLF, SF ;
OGARRA, A ;
MURPHY, KM .
SCIENCE, 1993, 260 (5107) :547-549
[10]  
HUNTER CA, 1995, IMMUNOLOGY, V84, P16