The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus
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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)γ, tumour necrosis factor-α and interleukin (IL)-1β, 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 IFNγ 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 IFNγ 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.
KeywordsTuberculosis Cytokine Production Glycaemic Control Diabetic Subject Tuberculosis Sonicate
This study is an indirect result of the project “Immunogenetic basis of susceptibility to and disease manifestations of mycobacterial infectious”, conducted within the ‘Scientific Programme Indonesia Netherlands’ (SPIN) and supported by the Royal Academy of Arts and Sciences (KNAW), Netherlands, and the Poverty Related Infection Oriented Research (PRIOR) funded by NWO-WOTRO. Funding was provided by the KNAW (mobility grant), the Doctor Catharina van Tussenbroek Foundation, the Janssens Foundation, and the Nederlandse Vereniging voor Immunologie (NVVI), all from the Netherlands. We thank Frenita Siagian and Genia Soemitro for their efforts in subject management and obtaining blood samples. We also extend our gratitude to Dr. Halim Danusantoso and the staff from the Indonesian Tuberculosis Control Association, Jakarta Branch, Indonesia, and Prof. Sangkot Marzuki, director of the Eijkman Institute of Molecular Biology, Jakarta, for their kind support in this collaborative project.
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