The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus

Abstract

As patients with diabetes mellitus are at increased risk of developing tuberculosis, we hypothesized that this susceptibility to mycobacterial infection is due to a defective Th1-cytokine response. To explore this hypothesis, we examined four groups of subjects in Indonesia: 23 patients with tuberculosis, 34 patients with tuberculosis and diabetes, 32 patients with diabetes only and 36 healthy controls. Ex-vivo production of interferon (IFN)gamma, tumour necrosis factor-alpha and interleukin (IL)-1beta, 6, 10, -12 and -4 was measured following stimulation with Mycobacterium tuberculosis, Escherichia coli lipopolysaccharide and phytohaemagglutinin. Patients with active tuberculosis were found to have lower IFNgamma levels and a higher production of other pro-inflammatory cytokines and IL-4, both in the presence and absence of diabetes. Diabetes patients without tuberculosis, however, showed strongly reduced non-specific IFNgamma production, which is essential for inhibition of the initial growth of M. tuberculosis. Our data suggest that a defective non-specific immune response in diabetes may contribute to an increased susceptibility to develop tuberculosis.

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

“…Several early studies reported reduced proinflammatory cytokines in patients with diabetes after infection with Mycobacterium tuberculosis (3,4). Two studies, however, reported the elevation of helper T-cell type 1 (Th1) cytokines in tuberculosis-infected diabetic hosts; one was conducted in streptozocin-treated mice (5) and another in diabetic and nondiabetic patients with tuberculosis (6).…”

Predictors of Outcome in Drug Resistant Tuberculosis Patients

“…On the other hand, many studies have found 2.1 to 8.8 times increased the risk of MDR-TB among diabetic TB patients [19,[32][33][34][35]. In addition, observational studies from Israel, Georgia, and Mexico have also shown patients with DM had a higher risk of developing MDR-TB [14,15,36].…”

“…Both mouse and human models have demonstrated that DM alters adaptive and cell-mediated immune responses [14][15][16]. Impaired alveolar macrophage activation due to glycation of binding sites may inhibit subsequent granuloma formation in TB-DM patients [17].…”

Outcome and mortality analysis in complicated parapneumonic effusion and empyema

“…Both mouse and human models have demonstrated that DM alters adaptive and cell-mediated immune responses. [18][19][20] Impaired alveolar macrophage activation due to glycation of binding sites may inhibit subsequent granuloma formation in TB-DM patients. 21 Chronic hyperglycemia may disrupt the regulation of key cytokines, such as interferon-gamma, which in turn may increase the M. tuberculosis bacterial burden and subsequent risk of death in TB-DM patients.…”

“…Both mouse and human models have demonstrated that DM alters adaptive and cell-mediated immune responses. [18][19][20] Impaired alveolar macrophage activation due to glycation of binding sites may inhibit subsequent granuloma formation in TB-DM patients. …”