PMID- 18645574
OWN - NLM
STAT- MEDLINE
DCOM- 20090327
LR  - 20090915
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Linking)
VI  - 32
IP  - 9
DP  - 2008 Sep
TI  - Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus.
PG  - 1407-14
LID - 10.1038/ijo.2008.109 [doi]
AB  - OBJECTIVE: Interleukin-18 (IL-18) has been recently demonstrated to improve 
      experimental hyperphagia and insulin resistance. Paradoxically, concentrations of 
      circulating IL-18 in obese subjects and in patients with type 2 diabetes are 
      increased. The objective of this study is to provide an explanation for this 
      paradox. DESIGN: We have hypothesized that cells from obese individuals or from 
      patients with type 2 diabetes mellitus have a diminished response to stimulation 
      with IL-18. IL-18 responsiveness was tested by stimulating blood monocytes of 
      obese or diabetes patients with rIL-18 or microbial components. RESULTS: Obese 
      individuals and patients with type 2 diabetes mellitus exhibit increased 
      circulating concentrations of IL-18. More importantly, leukocytes isolated from 
      obese or type 2 diabetes patients respond poorly after stimulation with IL-18, as 
      reflected by defective interferon-gamma (IFN gamma) production. The defective 
      response to IL-18 stimulation was accompanied by a 50% reduction in the 
      expression of IL-18R alpha and beta chains. In addition, cells of patients with 
      obesity and diabetes displayed an impaired release of IFN gamma after challenge 
      with bacterial or fungal pathogens, which was due to defective IL-18-mediated 
      signaling. CONCLUSION: Patients with obesity or type 2 diabetes mellitus are 
      characterized by lower responses after stimulation with IL-18. This IL-18 
      resistance explains the association of obesity and diabetes with high IL-18 
      circulating concentrations, similar to hyperinsulinemia and hyperleptinemia. 
      IL-18 resistance may represent an important mechanism of the increased 
      susceptibility of these patients to a number of infections.
FAU - Zilverschoon, G R C
AU  - Zilverschoon GR
AD  - Department of General Internal Medicine, Radboud University Nijmegen Medical 
      Center, Nijmegen, The Netherlands.
FAU - Tack, C J
AU  - Tack CJ
FAU - Joosten, L A B
AU  - Joosten LA
FAU - Kullberg, B J
AU  - Kullberg BJ
FAU - van der Meer, J W M
AU  - van der Meer JW
FAU - Netea, M G
AU  - Netea MG
LA  - eng
GR  - DK069881/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080722
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (Interleukin-18)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Recombinant Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Candida albicans/immunology
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 2/*immunology
MH  - Female
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-18/blood/*immunology
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/immunology
MH  - Obesity/*immunology
MH  - Recombinant Proteins/immunology
MH  - Staphylococcus aureus/immunology
MH  - Thinness/immunology
EDAT- 2008/07/23 09:00
MHDA- 2009/03/28 09:00
CRDT- 2008/07/23 09:00
PHST- 2008/07/23 09:00 [pubmed]
PHST- 2009/03/28 09:00 [medline]
PHST- 2008/07/23 09:00 [entrez]
AID - ijo2008109 [pii]
AID - 10.1038/ijo.2008.109 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2008 Sep;32(9):1407-14. doi: 10.1038/ijo.2008.109. Epub 2008 
      Jul 22.