Lymphocyte stimulation test in the diagnostics of adverse reactions to antituberculouse line 1 and 2 drugs.

Adverse drug reactions to anti-TB drugs (ADR) are found in 6-20% of patients and have various clinical manifestations and are detected in the lymphocyte stimulation test (LST), recorded by the incorporation on H3 thymidine, but nowadays it has significant limitations. We used LST with WST-1 reagent to detect ADR to the main 1-st and 2-nd line antituberculosis drugs in 11 tuberculosis patients who had ADR (6 - hepatotoxic reaction, 3 - blood eosinophilia and 2 - with joint pain syndrome). 6 people with tuberculosis contacts made up the control group. LST evaluation with WST-1 showed that in patients with a hepatotoxic reaction, the SI index was>2 and exceeded the values in the control group (3.28±0.59, 95% CI-1.16 and 0, 74±0.16, 95% CI - 0.31, respectively) upon stimulation of cell cultures with rifampicin alone but not with other drugs. Cell cultures stimulated with the PHA mitogen have SI >2 in ADR patients (mainly with hepatotoxic reactions). Control group SI was <2 (4,93±0.53, 95% CI - 1, 04 and 1.97±0.3, 95% CI - 0.59, respectively). We have not detected PPD-L cell cultures stimulation with WST-1 reagent both in the group of patients with ADR and the control group. In patients with eosinophilia and joint pain syndrome SI was low for all studied drugs and did not differ from the control group. The sensitivity of the LST test with WST-1 reagent is not sufficient to determine ADR to anti-TB drugs.

Local targeting NF-κB in the lung tissue of TB-infected mice diminishes the level of pathology.

Mice of the genetically TB-susceptible strain I/St were infected with ∼100 CFU of Mycobacterium tuberculosis strain H37Rv, and after week 3 post-infection treated by inhalations of the NBD peptide selectively blocking NF-κB activation pathway. This therapy resulted in a pronounced attenuation of lung pathology and down-regulation of the expression of several genes encoding major inflammatory molecules, but did not diminish the level of mycobacterial multiplication in the lungs.

Host genetics in granuloma formation: human-like lung pathology in mice with reciprocal genetic susceptibility to M. tuberculosis and M. avium.

Development of lung granulomata is a hallmark of infections caused by virulent mycobacteria, reflecting both protective host response that restricts infection spreading and inflammatory pathology. The role of host genetics in granuloma formation is not well defined. Earlier we have shown that mice of the I/St strain are extremely susceptible to Mycobacterium tuberculosis but resistant to M. avium infection, whereas B6 mice show a reversed pattern of susceptibility. Here, by directly comparing: (i) characteristics of susceptibility to two infections in vivo; (ii) architecture of lung granulomata assessed by immune staining; and (iii) expression of genes encoding regulatory factors of neutrophil influx in the lung tissue, we demonstrate that genetic susceptibility of the host largely determines the pattern of lung pathology. Necrotizing granuloma surrounded by hypoxic zones, as well as a massive neutrophil influx, develop in the lungs of M. avium-infected B6 mice and in the lungs of M. tuberculosis-infected I/St mice, but not in the lungs of corresponding genetically resistant counterparts. The mirror-type lung tissue responses to two virulent mycobacteria indicate that the level of genetic susceptibility of the host to a given mycobacterial species largely determines characteristics of pathology, and directly demonstrate the importance of host genetics in pathogenesis.