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

Abstract

SUMMARYEarlier 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 (TGFb), nitric oxide and tumour necrosis factor-alpha (TNF-a ) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-g), IL-4, IL-12, TGF-b , TNF-a 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-g, TGF-b and TNF-a production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-g were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-b and TNF-a 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.

Cattle Husbandry in Ethiopia Is a Predominant Factor Affecting the Pathology of Bovine Tuberculosis and Gamma Interferon Responses to Mycobacterial Antigens

“…In addition, the proportion of the animals kept indoors that had more severe disease and higher pathology scores displayed lower IFN-␥ responses than the animals kept in a pasture and the lesions of these pastured Holstein cattle were relatively mild or contained. These latter findings are therefore more in line with those of other studies that described changes in the nature of the immune responses with disease progression, from a dominant Th1-type response at early stages of disease toward B-cell antibody production and lower T-cell responses at more-progressive disease stages (5,9,11,15,18,19,20), or a positive correlation between antibody responses and pathology (22,27,31). A consequence of lower cell-mediated immune responses in animals with severe disease could be their escape from detection by cell-mediated immune response-based tests like the IFN-␥ test.…”

Impaired Gamma Interferon Response to Mycobacterium vaccae Antigens in Patients with Cavitary Pulmonary Tuberculosis

“…2). Although the specific cytokine response against M. vaccae antigens in cavitary and noncavitary TB patients has not been studied before, diminished Th1 responses to M. tuberculosis antigens in PBMC from TB patients have been directly correlated with the severity of the disease (2,8,13,15). Our findings further support these previous observations (Fig.…”

Nitrite produced byMycobacterium tuberculosisin human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression

“…Last, the shared regulation of genes by nitrate and by the potentially mycobactericidal conditions of iron restriction and exposure to acid and hydrogen peroxide suggests that nitrate respiration may benefit Mtb in vivo by preparing it to withstand the latter stresses. Nitrite is highly diffusible, as evidenced by its accumulation in the plasma of Mtb-infected individuals (53,54). Endogenously produced nitrite may diffuse within infected tissue and contribute to a preemptive induction of Mtb genes that benefit Mtb's survival in a hostile host environment.…”