PMID- 11083816
OWN - NLM
STAT- MEDLINE
DCOM- 20001213
LR  - 20240407
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 68
IP  - 12
DP  - 2000 Dec
TI  - Interleukin-18 (IL-18) enhances innate IL-12-mediated resistance to Toxoplasma 
      gondii.
PG  - 6932-8
AB  - Innate resistance to Toxoplasma gondii is dependent on the ability of 
      interleukin-12 (IL-12) to stimulate natural killer (NK) cell production of gamma 
      interferon (IFN-gamma). Since IL-18 is a potent enhancer of IL-12-induced 
      production of IFN-gamma by NK cells, SCID mice (which lack an adaptive immune 
      response) were used to assess the role of IL-18 in innate resistance to T. 
      gondii. Administration of anti-IL-18 to SCID mice infected with T. gondii 
      resulted in an early reduction in serum levels of IFN-gamma but did not 
      significantly decrease resistance to this infection. In contrast, administration 
      of exogenous IL-18 to infected SCID mice resulted in increased production of 
      IFN-gamma, reduced parasite burden, and a delay in time to death. The protective 
      effects of IL-18 treatment correlated with increased NK cell numbers and 
      cytotoxic activity at the local site of administration and with elevated levels 
      of inducible nitrous oxide synthose in the spleens of treated mice. In addition, 
      in vivo depletion studies demonstrated that the ability of exogenous IL-18 to 
      enhance resistance to T. gondii was dependent on IL-12, IFN-gamma, and NK cells. 
      Together, these studies demonstrate that although endogenous IL-18 appears to 
      have a limited role in innate resistance to T. gondii, treatment with IL-18 can 
      augment NK cell-mediated immunity to this pathogen.
FAU - Cai, G
AU  - Cai G
AD  - Department of Pathobiology, School of Veterinary Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania 19104-6008, USA.
FAU - Kastelein, R
AU  - Kastelein R
FAU - Hunter, C A
AU  - Hunter CA
LA  - eng
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - R01 AI042334/AI/NIAID NIH HHS/United States
GR  - AI 42334-01/AI/NIAID NIH HHS/United States
GR  - P30 DK50306/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Interleukin-18)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-12/*physiology
MH  - Interleukin-18/*physiology
MH  - Killer Cells, Natural/immunology
MH  - Mice
MH  - Mice, SCID
MH  - Toxoplasmosis, Animal/*immunology
PMC - PMC97801
EDAT- 2000/11/18 11:00
MHDA- 2001/02/28 10:01
PMCR- 2000/12/01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - 0390 [pii]
AID - 10.1128/IAI.68.12.6932-6938.2000 [doi]
PST - ppublish
SO  - Infect Immun. 2000 Dec;68(12):6932-8. doi: 10.1128/IAI.68.12.6932-6938.2000.