title: 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.
authors.affiliation: Department of Internal Medicine, Radboud University Nijmegen Medical Center, 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: J E
authors.initials: JE
authors.lastname: Stalenhoef
authors.forename: B
authors.initials: B
authors.lastname: Alisjahbana
authors.forename: E J
authors.initials: EJ
authors.lastname: Nelwan
authors.forename: J
authors.initials: J
authors.lastname: van der Ven-Jongekrijg
authors.forename: T H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: J W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: R H
authors.initials: RH
authors.lastname: Nelwan
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: R
authors.initials: R
authors.lastname: van Crevel
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006801:Humans; D007214:Indonesia; D007371:Interferon-gamma / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012306:Risk; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D007371:Interferon-gamma