Take a look at the following references:

Tumor necrosis factor-α is required in the protective immune response against mycobacterium tuberculosis in mice

 Immunity Volume 2, Issue 6, June 1995, Pages 561–572

JoAnne L. Flynn1,

Marsha M. Goldstein2,

John Chan3,

Karla J. Triebold4,

Klaus Pfeffer5, 6,

Charles J. Lowenstein7,

Robert Schrelber8,

Tak W. Mak5,

Barry R. Bloom4

Abstract

Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-α (TNFα) contributes to this disease using murine models In which the action of TNFα is inhibited. TNFa was neutralized In vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55 kDa TNF receptor was used. The data from both models established that TNFα and the 55 kDa TNF receptor are essential for protection against tuberculosis in mice, and for reactive nitrogen production by macrophages early in infection. Granulomas were formed in equal numbers in control and experimental mice, but necrosis was observed only in mice deficient in TNFα or TNF receptor. TNFα and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed.

Activities of Several Novel Oxazolidinones againstMycobacterium tuberculosis in a Murine Model

Antimicrob. Agents Chemother. May 1999 vol. 43 no. 5 1189-1191                                    

M. H. Cynamon*,

S. P. Klemens,

C. A. Sharpe, and

S. Chase

ABSTRACT

The activities of linezolid, eperezolid, and PNU-100480 were evaluated in a murine model of tuberculosis. Approximately 107 viable Mycobacterium tuberculosis ATCC 35801 organisms were given intravenously to 4-week-old outbred CD-1 mice. In the first study, treatment was started 1 day postinfection and was given by gavage for 4 weeks. Viable cell counts were determined from homogenates of spleens and lungs. PNU-100480 was as active as isoniazid. Linezolid was somewhat less active than PNU-100480 and isoniazid. Eperezolid had little activity in this model. In the next two studies, treatment was started 1 week postinfection. A dose-response study was performed with PNU-100480 and linezolid (both at 25, 50, and 100 mg/kg of body weight). PNU-100480 was more active than linezolid, and its efficacy increased with an escalation of the dose. Subsequently, the activity of PNU-100480 alone and in combination with rifampin or isoniazid was evaluated and was compared to that of isoniazid-rifampin. The activity of PNU-100480 was similar to that of isoniazid and/or rifampin in the various combinations tested. Further evaluation of these oxazolidinones in the murine test system would be useful prior to the development of clinical studies with humans.

Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis.

Infect. Immun. February 1995 vol. 63 no. 2 736-740                                    

J Chan,

K Tanaka,

D Carroll,

J Flynn, and

B R Bloom

ABSTRACT

We have recently demonstrated that the macrophage L-arginine-dependent cytotoxic pathway effectively kills the virulent Erdman strain of Mycobacterium tuberculosis in vitro via the generation of toxic reactive nitrogen intermediates by the enzyme nitric oxide synthase. This report demonstrates that two distinct inhibitors of nitric oxide synthase (aminoguanidine and NG-monomethyl-L-arginine) render similar deleterious effects on tuberculous infection in mice, as assessed by mortality, bacterial burden, and pathological tissue damage, thus confirming the importance of reactive nitrogen intermediates in resistance against M. tuberculosis.

Thank you very much Dr. Lawrence and Amar