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

• DOI: 10.1007/s10096-007-0395-0
• Publication Date: 2007-10-25T10:30:30Z
• Authors: J. E. Stalenhoef; B. Alisjahbana; E. J. Nelwan; J. Ven-Jongekrijg; T. H. M. Ottenhoff; J. W. M. Meer; R. H Nelwan; M. G. Netea; R. Crevel
• Keywords: Adult; Male; Risk; 0301 basic medicine; NCMLS 1: Infection and autoimmunity; NCMLS 1: Immunity, infection and tissue repair; N4i 1: Pathogenesis and modulation of inflammation; N4i 3: Poverty-related infectious diseases; Middle Aged; NCEBP 13: Infectious diseases and international health; 3. Good health; Diabetes Complications; Interferon-gamma; 03 medical and health sciences; N4i 2: Invasive mycoses and compromised host; Diabetes Mellitus, Type 2; Indonesia; Leukocytes, Mononuclear; Humans; Tuberculosis; UMCN 4.1: Microbial pathogenesis and host defense; Female; Disease Susceptibility; Cells, Cultured

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.