In vitro synthesis of interferon-γ, interleukin-4, transforming growth factor-β and interleukin-1β by peripheral blood mononuclear cells from tuberculosis patients:: Relationship with the severity of pulmonary involvement

Given the role of cell-mediated immune responses in resistance to mycobacteria, we sought to analyse whether there was a relationship between the severity of pulmonary tuberculosis (TB) and lymphocyte proliferation as well as in vitro, cytokine production. To achieve this, 25 untreated TB patients showing mild (n = 5), moderate (n = 9) or advanced (n = 11) pulmonary disease, and 12, age-matched healthy controls (mean +/- SD, 37 +/- 14.5 years) were studied. Peripheral blood mononuclear cells were cultured for 5 days with 10 mu g/ml whole, sonicated Mycobacterium tuberculosis (WSA) or 2.5 mu g/ml Concanavalin A (Con A). Supernatants were collected on day 4, from cultures grown with or without WSA, for measurement of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-1 beta and transforming growth factor-beta (TGF-beta). Antigen-specific proliferation was found to be reduced among patients and more profound in those with advanced disease who also displayed a depressed response to Con A. Patients with mi Id TB showed a preferential production of IFN-gamma over IL-4, gave the highest level of IFN-gamma synthesis upon specific antigen stimulation and showed increased levels of IL-1 beta production. Findings in patients with moderate TB appeared compatible with a mixed production of IFN-gamma and IL-4 coexisting with a higher synthesis of TGF-beta, by comparison to patients with mild TB. Advanced disease showed the highest IL-4 and TGF-beta production, with IFN-gamma synthesis readily noticeable, yet decreased in comparison with the other patient groups, Differences in cytokine response according to the amount of lung involvement suggest a role for such mediators in the immunopathogenesis underlying the distinct clinical forms of pulmonary TB, that is a predominant T helper (Th)l-like or Th2-like activity in mild or in progressive TB, respectively.