PMID- 11069090
OWN - NLM
STAT- MEDLINE
DCOM- 20001207
LR  - 20041117
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 30
IP  - 10
DP  - 2000 Oct
TI  - Interleukin-18 induces production of proinflammatory cytokines in mice: no 
      intermediate role for the cytokines of the tumor necrosis factor family and 
      interleukin-1beta.
PG  - 3057-60
AB  - Interleukin-18 (IL-18) is not only a co-stimulus for the induction of 
      interferon-gamma but also has direct proinflammatory effects by inducing tumor 
      necrosis factor-alpha (TNF-alpha), IL-1, IL-8 and IL-6. However, the cascade of 
      events leading to induction of cytokines by IL-18 is unclear. The aim of the 
      present study was to investigate whether murine IL-18 stimulates production of 
      proinflammatory cytokines, and to assess whether induction of second-wave 
      cytokines such as IL-6 by IL-18 is driven by intermediary induction of endogenous 
      cytokines of the TNF family or IL-1beta. When mouse peritoneal macrophages were 
      stimulated in vitro with recombinant murine IL-18, there was a dose-dependent 
      induction of TNF, IL-1alpha, and IL-1beta. IL-6 synthesis was also strongly 
      induced by IL-18 and, as revealed by studies in knockout mice, this production 
      was not dependent on interactions between endogenous cytokines of the TNF/TNF 
      receptor family: TNF-alpha, lymphotoxin-alpha, Fas/Fas ligand (L) or CD40/CD40L. 
      Moreover, the induction of IL-6 was also independent of endogenous IL-1beta, as 
      macrophages isolated from IL-1beta deficient mice produced normal amounts of IL-6 
      after stimulation with IL-18. In conclusion, murine IL-18 has pleiotropic 
      proinflammatory activities by inducing production of TNF-alpha, IL-1alpha, 
      IL-1beta and IL-6, which could have important consequences for the 
      pathophysiology of infectious and autoimmune diseases.
FAU - Netea, M G
AU  - Netea MG
AD  - Department of Medicine, University Hospital Nijmegen, The Netherlands. 
      M.Netea@aig.azn.nl
FAU - Kullberg, B J
AU  - Kullberg BJ
FAU - Verschueren, I
AU  - Verschueren I
FAU - Van Der Meer, J W
AU  - Van Der Meer JW
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-6)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cytokines/*biosynthesis/classification/genetics
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*drug effects
MH  - Inflammation/genetics/*metabolism
MH  - Interleukin-1/biosynthesis/deficiency/genetics/physiology
MH  - Interleukin-18/pharmacology/*physiology
MH  - Interleukin-6/biosynthesis/genetics
MH  - Macrophages, Peritoneal/drug effects/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multigene Family
MH  - Recombinant Proteins/pharmacology
MH  - Specific Pathogen-Free Organisms
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics/physiology
EDAT- 2000/11/09 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
AID - 10.1002/1521-4141(200010)30:10<3057::AID-IMMU3057>3.0.CO;2-P [doi]
PST - ppublish
SO  - Eur J Immunol. 2000 Oct;30(10):3057-60. doi: 
      10.1002/1521-4141(200010)30:10<3057::AID-IMMU3057>3.0.CO;2-P.