The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus.
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.
Stalenhoef
J E
JE
Department of Internal Medicine, Radboud University Nijmegen Medical Center, 9101, 6500 HB Nijmegen, The Netherlands.
Alisjahbana
B
B
Nelwan
E J
EJ
van der Ven-Jongekrijg
J
J
Ottenhoff
T H M
TH
van der Meer
J W M
JW
Nelwan
R H
RH
Netea
M G
MG
van Crevel
R
R
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*
D007371:Interferon-gamma