Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB)

Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-beta), nitric oxide and tumour necrosis factor-alpha (TNF-alpha) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-gamma), IL-4, IL-12, TGF-beta, TNF-alpha and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 +/- 13 years (mean +/- s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-gamma, TGF-beta and TNF-alpha production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-gamma were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-beta and TNF-alpha concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease.