| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
The intracellular pathogen Mycobacterium avium is a
major cause of opportunistic infection in AIDS patients and is
difficult to manage using conventional chemotherapeutic approaches. In
the current study, we describe a strategy for the treatment of M.
avium in T cell-deficient hosts based on the simultaneous
administration of antibiotics and the immunomodulatory cytokine IL-12.
In contrast to SCID mice, which were partially resistant, animals
lacking a functional IL-12 p40 gene were found to be highly
susceptible to M. avium infection, suggesting that the
cytokine can control bacterial growth even in immunodeficient mice.
Indeed, rIL-12 that was injected into infected SCID mice in high doses
caused small but significant reductions in splenic pathogen loads.
Moreover, a lower dose of IL-12, when combined with the
antimycobacterial drugs clarithromycin or rifabutin, induced a decrease
in bacterial numbers that was significantly greater than that resulting
from the administration of the cytokine or drug alone. A similar
synergistic effect of IL-12 and antibiotics was seen when
immunocompetent mice were treated with the same regimen. The activity
of IL-12 in these experiments was shown to be dependent upon the
induction of endogenous IFN-
. Nevertheless, IFN- itself, even
when given at a higher dose than IL-12, failed to significantly enhance
antibiotic clearance of bacteria. Together these findings suggest that
IL-12 may be a particularly potent adjunct for chemotherapy of M.
avium infection in immunocompromised individuals and may result
in more effective control of the pathogen without the need for
increased drug dosage.
This article has been cited by other articles:
|
|
 |
|
  S. Fuschillo, A. De Felice, and G. Balzano Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms Eur. Respir. J., February 1, 2008; 31(2): 396 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Salvatore, M. Fonseca-Aten, K. Katz-Gaynor, A. M. Gomez, and R. D. Hardy Intranasal Interleukin-12 Therapy Inhibits Mycoplasma pneumoniae Clearance and Sustains Airway Obstruction in Murine Pneumonia Infect. Immun., February 1, 2008; 76(2): 732 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Feng, M. Kaviratne, A. G. Rothfuchs, A. Cheever, S. Hieny, H. A. Young, T. A. Wynn, and A. Sher NK Cell-Derived IFN-{gamma} Differentially Regulates Innate Resistance and Neutrophil Response in T Cell-Deficient Hosts Infected with Mycobacterium tuberculosis J. Immunol., November 15, 2006; 177(10): 7086 - 7093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Field and R. L. Cowie Lung Disease Due to the More Common Nontuberculous Mycobacteria Chest, June 1, 2006; 129(6): 1653 - 1672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Pammit, V. N. Budhavarapu, E. K. Raulie, K. E. Klose, J. M. Teale, and B. P. Arulanandam Intranasal Interleukin-12 Treatment Promotes Antimicrobial Clearance and Survival in Pulmonary Francisella tularensis subsp. novicida Infection Antimicrob. Agents Chemother., December 1, 2004; 48(12): 4513 - 4519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Field, D. Fisher, and R. L. Cowie Mycobacterium avium complex Pulmonary Disease in Patients Without HIV Infection Chest, August 1, 2004; 126(2): 566 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Nolt and J. L. Flynn Interleukin-12 Therapy Reduces the Number of Immune Cells and Pathology in Lungs of Mice Infected with Mycobacterium tuberculosis Infect. Immun., May 1, 2004; 72(5): 2976 - 2988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bafica, C. A. Scanga, M. L. Schito, S. Hieny, and A. Sher Cutting Edge: In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2 J. Immunol., August 1, 2003; 171(3): 1123 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fieschi, S. Dupuis, E. Catherinot, J. Feinberg, J. Bustamante, A. Breiman, F. Altare, R. Baretto, F. Le Deist, S. Kayal, et al. Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor {beta}1 Deficiency: Medical and Immunological Implications J. Exp. Med., February 17, 2003; 197(4): 527 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Greenwell-Wild, N. Vazquez, D. Sim, M. Schito, D. Chatterjee, J. M. Orenstein, and S. M. Wahl Mycobacterium avium Infection and Modulation of Human Macrophage Gene Expression J. Immunol., December 1, 2002; 169(11): 6286 - 6297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Nau, J. F. L. Richmond, A. Schlesinger, E. G. Jennings, E. S. Lander, and R. A. Young Human macrophage activation programs induced by bacterial pathogens PNAS, January 17, 2002; (2002) 22649799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hesse, M. Modolell, A. C. La Flamme, M. Schito, J. M. Fuentes, A. W. Cheever, E. J. Pearce, and T. A. Wynn Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of L-Arginine Metabolism J. Immunol., December 1, 2001; 167(11): 6533 - 6544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashi, S. P. Rao, K. Takabayashi, J. H. Van Uden, R. S. Kornbluth, S. M. Baird, M. W. Taylor, D. A. Carson, A. Catanzaro, and E. Raz Enhancement of Innate Immunity against Mycobacterium avium Infection by Immunostimulatory DNA Is Mediated by Indoleamine 2,3-Dioxygenase Infect. Immun., October 1, 2001; 69(10): 6156 - 6164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Silva, T. F. Pais, and R. Appelberg Blocking the Receptor for IL-10 Improves Antimycobacterial Chemotherapy and Vaccination J. Immunol., August 1, 2001; 167(3): 1535 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Nagabhushanam and C. Cheers Non-Major Histocompatibility Complex Control of Antibody Isotype and Th1 versus Th2 Cytokines during Experimental Infection of Mice with Mycobacterium avium Infect. Immun., March 1, 2001; 69(3): 1708 - 1713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mohagheghpour, A. van Vollenhoven, J. Goodman, and L. E. Bermudez Interaction of Mycobacterium avium with Human Monocyte-Derived Dendritic Cells Infect. Immun., October 1, 2000; 68(10): 5824 - 5829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Doherty, C. Chougnet, M. Schito, B. K. Patterson, C. Fox, G. M. Shearer, G. Englund, and A. Sher Infection of HIV-1 Transgenic Mice with Mycobacterium avium Induces the Expression of Infectious Virus Selectively from a Mac-1-Positive Host Cell Population J. Immunol., August 1, 1999; 163(3): 1506 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shimizu, H. Tomioka, K. Sato, C. Sano, T. Akaki, S. Dekio, Y. Yamada, T. Kamei, H. Shibata, and N. Higashi Effects of the Chinese Traditional Medicine Mao-Bushi-Saishin-To on Therapeutic Efficacy of a New Benzoxazinorifamycin, KRM-1648, against Mycobacterium avium Infection in Mice Antimicrob. Agents Chemother., March 1, 1999; 43(3): 514 - 519. [Abstract] [Full Text]
|
|
|
|
|
|
K. Mohan, H. Sam, and M. M. Stevenson Therapy with a Combination of Low Doses of Interleukin 12 and Chloroquine Completely Cures Blood-Stage Malaria, Prevents Severe Anemia, and Induces Immunity to Reinfection Infect. Immun., February 1, 1999; 67(2): 513 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Silva, T. F. Pais, and R. Appelberg Evaluation of IL-12 in Immunotherapy and Vaccine Design in Experimental Mycobacterium avium Infections J. Immunol., November 15, 1998; 161(10): 5578 - 5585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Nau, J. F. L. Richmond, A. Schlesinger, E. G. Jennings, E. S. Lander, and R. A. Young Human macrophage activation programs induced by bacterial pathogens PNAS, February 5, 2002; 99(3): 1503 - 1508. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
