Kim West

Diabetes mellitus (DM) increases risk for pulmonary tuberculosis (TB) and adverse treatment outcomes. Systemic hyper-inflammation is characteristic in people with TB and concurrent DM (TBDM) at baseline, but the impact of TB treatment on this pattern has not been determined. We measured 17 plasma cytokines and growth factors in longitudinal cohorts of Indian and Brazilian pulmonary TB patients with or without DM. Principal component analysis revealed virtually complete separation of TBDM from TB individuals in both cohorts at baseline, with hyper-inflammation in TBDM that continued through treatment completion at six months. By one year after treatment completion, there was substantial convergence of mediator levels between groups within the India cohort. Non-resolving systemic inflammation in TBDM comorbidity could reflect delayed lesion sterilization or non-resolving sterile inflammation. Either mechanism portends unfavorable long-term outcomes including risk for recurrent TB and for damaging immune pathology.

Sirtuin 1 activation decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis .

The efficiency of prime-boost vaccinations on the induction of T-cell responses to Sin Nombre virus nucleocapsid protein expressed by recombinant vaccinia virus, replication-deficient adenovirus, and plasmid DNA in mice was quantitated by the number of epitope-specific interferon-γ–producing T cells and cytotoxic T-lymphocyte activity induced. In prime-boost immunizations, all combinations that included the recombinant adenovirus induced a much higher number of epitope-specific interferon-γ–producing T cells than did other combinations. A single immunization of the recombinant adenovirus was able to induce similarly high levels of epitope-specific interferon-γ–producing cells, despite the fact that the recombinant adenovirus produces less amount of the Sin Nombre virus nucleocapsid protein.

Administration of rimantadine to mice via drinking water, following a prophylactic dose, reduced lung virus titers by >3 log₁₀ plague-forming units (pfu)/ml but caused only marginal reductions in lung virus titers when therapy wasstarted 8 h after exposure to virus. Mice given rimantadine prophylactically plus therapeutically were resistant to rechallenge with virus at a dose equivalent to that used for the primary infection (SO pfu/mouse) but not to a high dose (1 × 10⁵ pfu/mouse). VIrUS-neutralizing-antibody titers were reduced only by rimantadine treatment, which included prophylaxis, whereas the cytotoxic T lymphocyte (CTL) response was depressed by treatment givenwith or without prophylaxis.Miceinfected with rimantadine-resistant virus had no decrease in CTL or antibody responses when treated with rimantadine. Therefore, the depression in CTL and antibody responses associated with rimantadine treatment appears to bedue to a decrease in the amount of viral antigen available or interference with viral antigen processing and not to nonspecific immunosuppressive effects.