| IL-12 promotes drug-induced clearance of Mycobacterium avium infection in mice. | |
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MedLine Citation:
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PMID: 9605144 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-gamma. Nevertheless, IFN-gamma 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. |
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Authors:
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T M Doherty; A Sher |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 160 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1998 Jun |
Date Detail:
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Created Date: 1998-06-11 Completed Date: 1998-06-11 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 5428-35 Citation Subset: AIM; IM; X |
Affiliation:
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Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Health, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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therapeutic use* Animals Clarithromycin / administration & dosage Crosses, Genetic Drug Therapy, Combination Immunity, Innate / drug effects, genetics Injections, Intraperitoneal Interferon-gamma / physiology, therapeutic use Interleukin-12 / deficiency, therapeutic use* Mice Mice, Inbred C57BL Mice, Knockout Mice, SCID Mycobacterium avium / immunology* Rifabutin / administration & dosage Tuberculosis / drug therapy*, immunology*, microbiology |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 187348-17-0/Interleukin-12; 72559-06-9/Rifabutin; 81103-11-9/Clarithromycin; 82115-62-6/Interferon-gamma |
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