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rdf:type |
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lifeskim:mentions |
umls-concept:C0012727,
umls-concept:C0015127,
umls-concept:C0025543,
umls-concept:C0025919,
umls-concept:C0041327,
umls-concept:C0079189,
umls-concept:C0087111,
umls-concept:C0332464,
umls-concept:C1314792,
umls-concept:C1517004,
umls-concept:C1608879,
umls-concept:C1979963,
umls-concept:C1999216,
umls-concept:C2003903,
umls-concept:C2827424
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pubmed:issue |
3
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pubmed:dateCreated |
2000-9-26
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pubmed:abstractText |
BB-94 (batimastat) is a broad- spectrum hydroxamic acid-based zinc metalloproteinase inhibitor that inhibits both the matrix metalloproteinases (MMP) and members of the ADAM family of enzymes such as Tumour Necrosis Factor-alpha Cleaving Enzyme (TACE). These enzymes are involved in the regulation of inflammatory processes in tuberculosis. Balb/c mice infected with M. tuberculosis via the intratracheal route were treated with BB-94 for 1 month, starting on the day of infection. Immunohistochemistry, semiquantitative RT-PCR and ELISA assays for cytokines revealed a deficit in IL-1 and IL-2 expression and a premature bias towards IL-4 expression, accompanied by a delay in granuloma formation and more rapid progression of disease in BB-94-treated animals. This situation corrected itself after the drug was withdrawn at 28 days. In contrast, when BB-94 was administered only after 1 month there were no significant changes apart from the presence of amyloid, and a paradoxically increased expression of IL-1alpha. These results cast light on mechanisms of immunity in tuberculosis and also indicate that in patients treated with similar broad-spectrum MMP inhibitors there may be a risk of inappropriate deviation of some immune responses towards a Type-2 cytokine profile.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0959-9673
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
199-209
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10971741-Animals,
pubmed-meshheading:10971741-Antineoplastic Agents,
pubmed-meshheading:10971741-Cytokines,
pubmed-meshheading:10971741-Drug Administration Schedule,
pubmed-meshheading:10971741-Hypersensitivity, Delayed,
pubmed-meshheading:10971741-Interleukins,
pubmed-meshheading:10971741-Matrix Metalloproteinases,
pubmed-meshheading:10971741-Mice,
pubmed-meshheading:10971741-Mice, Inbred BALB C,
pubmed-meshheading:10971741-Phenylalanine,
pubmed-meshheading:10971741-Protease Inhibitors,
pubmed-meshheading:10971741-Survival Rate,
pubmed-meshheading:10971741-Thiophenes,
pubmed-meshheading:10971741-Tuberculosis, Pulmonary,
pubmed-meshheading:10971741-Zinc
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pubmed:year |
2000
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pubmed:articleTitle |
Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent metalloproteinases, causes deviation of the cytokine profile towards type-2 in experimental pulmonary tuberculosis in Balb/c mice.
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pubmed:affiliation |
Experimental Pathology Laboratory, Department of Pathology, Instituto Nacional de la Nutricion 'Salvador Zubiran', Mexico City, Mexico.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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