INHIBITION OF TUMOR-NECROSIS-FACTOR-ALPHA ALTERS RESISTANCE TO MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN MICE

Citation
S. Bala et al., INHIBITION OF TUMOR-NECROSIS-FACTOR-ALPHA ALTERS RESISTANCE TO MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN MICE, Antimicrobial agents and chemotherapy, 42(9), 1998, pp. 2336-2341
Citations number
36
Categorie Soggetti
Pharmacology & Pharmacy",Microbiology
ISSN journal
00664804
Volume
42
Issue
9
Year of publication
1998
Pages
2336 - 2341
Database
ISI
SICI code
0066-4804(1998)42:9<2336:IOTART>2.0.ZU;2-Z
Abstract
Increased production of tumor necrosis factor alpha (TNF-alpha) appear s to play an important role in the progression of human immunodeficien cy virus disease. One treatment strategy being explored is the use of TNF-alpha inhibitors. TNF-alpha also appears to be important in confer ring resistance to infections, and the inhibition of this cytokine may exacerbate the emergence of opportunistic pathogens, such as Mycobact erium avium complex (MAC). The present study examines the possibility that inhibition of TNF-alpha will increase the progression of disease in mice infected with MAC, C57BL/6 beige (bg/bg) mice have been shown to be highly susceptible to infection with MAC and are routinely used for testing of antimycobacterial drugs. However, bg/bg mice are known to exhibit impaired phagocyte and natural killer cell function, Since these cell types are important sources of TNF-alpha, the susceptibilit y of the bg/bg strain to infection with MAC was compared with those of the heterozygous (bg/+) and wild-type (+/+) strains of C57BL/6 mice. The susceptibilities of the bg/bg and bg/+ strains of mice infected wi th MAC were found to be comparable. The +/+ strain was the least susce ptible, Mycobacterial burden and serum TNF-alpha levels increased over time in all the strains of mice tested. The bg/+ strain of C57BL/6 mi ce was then chosen to measure the activity of TNF-alpha antagonists. T reatment with dexamethasone decreased serum TNF-alpha levels and incre ased mycobacterial burden. Treatment with anti-TNF-alpha antibody or p entoxifylline did not significantly alter serum TNF-alpha levels but i ncreased mycobacterial burden. Treatment with thalidomide neither cons istently altered mycobacterial burden in the spleens or livers of infe cted mice nor affected serum TNF-alpha levels.