PMID- 9490698
OWN - NLM
STAT- MEDLINE
DCOM- 19980409
LR  - 20220311
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 91
IP  - 6
DP  - 1998 Mar 15
TI  - Interleukin-18 regulation of interferon gamma production and cell proliferation 
      as shown in interleukin-1beta-converting enzyme (caspase-1)-deficient mice.
PG  - 2118-25
AB  - Interleukin-18 (IL-18) is a costimulatory factor for interferongamma (IFNgamma) 
      production. Processing of pro-IL-18 by IL-1beta-converting enzyme (ICE) leads to 
      the release of bioactive IL-18. Compared with wild-type (WT) mice, splenocytes 
      from ICE-deficient mice produced low IFNgamma after lipopolysaccharide (LPS) or 
      zymosan (50% and 80% reduction). In contrast, IFNgamma production was unimpaired 
      in ICE-deficient mice using Concanavalin A (Con A). Comparable results were 
      obtained when endogenous IL-18 was blocked with a neutralizing antibody. 
      LPS-induced IFNgamma was also reduced by an ICE inhibitor. Exogenous IL-18 
      augmented zymosan-induced IFNgamma production in WT mice. In ICE-deficient cells, 
      IFNgamma production was only partially restored by IL-18. The reduced levels of 
      IFNgamma in ICE-deficient mice were not due to a lack of IL-12, because zymosan 
      induced IL-12 equally in WT and in ICE-deficient mice. IFNgamma is an important 
      regulator of cell proliferation. In accordance, splenocytes from ICE-deficient 
      mice proliferated more when stimulated with LPS, but not with Con A. Furthermore, 
      in ovalbumin-sensitized ICE-deficient mice, proliferation of lymph node cells in 
      response to the specific antigen was not altered. Exogenous IFNgamma inhibited, 
      whereas blockade of endogenous IFNgamma or IL-18 increased, LPS induced 
      splenocyte proliferation both in WT and in ICE-deficient mice. Our results show 
      that IL-18 is an IL-12-independent regulator of IFNgamma production and of cell 
      proliferation induced by microbial stimuli. However, ICE-dependent processing of 
      IL-18 is not needed for response to mitogens or antigens.
FAU - Fantuzzi, G
AU  - Fantuzzi G
AD  - Division of Infectious Diseases, University of Colorado Health Sciences Center, 
      Denver, CO 80262, USA.
FAU - Puren, A J
AU  - Puren AJ
FAU - Harding, M W
AU  - Harding MW
FAU - Livingston, D J
AU  - Livingston DJ
FAU - Dinarello, C A
AU  - Dinarello CA
LA  - eng
GR  - AI-15614/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-18)
RN  - 0 (Lipopolysaccharides)
RN  - 11028-71-0 (Concanavalin A)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9006-59-1 (Ovalbumin)
RN  - 9010-72-4 (Zymosan)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Caspase 1
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Concanavalin A/pharmacology
MH  - Cysteine Endopeptidases/*deficiency/genetics/physiology
MH  - Cytokines/pharmacology/*physiology
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Immunization
MH  - Interferon-gamma/*biosynthesis/genetics
MH  - Interleukin-12/biosynthesis/genetics
MH  - Interleukin-18
MH  - Lipopolysaccharides/pharmacology
MH  - Lymph Nodes/cytology
MH  - Lymphocyte Activation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Ovalbumin/immunology
MH  - Polymerase Chain Reaction
MH  - Spleen/cytology
MH  - T-Lymphocytes/drug effects/*metabolism
MH  - Zymosan/pharmacology
EDAT- 1998/04/16 00:00
MHDA- 1998/04/16 00:01
CRDT- 1998/04/16 00:00
PHST- 1998/04/16 00:00 [pubmed]
PHST- 1998/04/16 00:01 [medline]
PHST- 1998/04/16 00:00 [entrez]
AID - S0006-4971(20)54813-1 [pii]
PST - ppublish
SO  - Blood. 1998 Mar 15;91(6):2118-25.