PMID- 10714558
OWN - NLM
STAT- MEDLINE
DCOM- 20000421
LR  - 20081121
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 20
IP  - 2
DP  - 2000 Feb
TI  - Interleukin-18 in combination with IL-2 enhances natural killer cell activity 
      without inducing large amounts of IFN-gamma in vivo.
PG  - 217-24
AB  - Interleukin-18 (IL-18) is known to synergistically enhance murine natural killer 
      (NK) cell activity in vitro when combined with either IL-12 or IL-2. However, it 
      has also been demonstrated that simultaneous administration of IL-18 and IL-12 to 
      mice induces extraordinarily large amounts of interferon-gamma (IFN-gamma) in the 
      serum. In this study, we examined the effects of a combination of IL-18 and IL-2 
      on in vivo NK cell activation in parallel with the induction of toxicity. In 
      contrast to the IL-18 and IL-12 combination, the combined administration of IL-18 
      and IL-2 to BALB/c mice for 3 days induced neither high levels of IFN-gamma 
      production nor other visible side effects. When compared with treatment with 
      IL-18 or IL-2 alone, the combined treatment resulted in a significant increase in 
      the number of DX-5 (pan-NK cells marker)-positive cells in spleens and a marked 
      enhancement of splenic NK activity, as determined by standard cytotoxicity 
      assays. Enhanced splenic cytotoxicity generated in the mice treated with both 
      IL-18 and IL-2 was also observed against syngeneic Colon 26 adenocarcinoma cells. 
      Consistent with this in vitro observation, combined treatment produced a 
      significantly stronger inhibitory effect on the pulmonary metastases following 
      i.v. injection of Colon 26 tumor cells than treatment with either cytokine alone. 
      These results suggest that IL-18 combined with IL-2 potentiates in vivo NK cell 
      activity and contributes to inhibition of tumor metastasis without inducing 
      significant toxicity.
FAU - Arai, N
AU  - Arai N
AD  - Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Okayama, Japan.
FAU - Akamatsu, S
AU  - Akamatsu S
FAU - Arai, S
AU  - Arai S
FAU - Toshimori, Y
AU  - Toshimori Y
FAU - Hanaya, T
AU  - Hanaya T
FAU - Tanimoto, T
AU  - Tanimoto T
FAU - Ikeda, M
AU  - Ikeda M
FAU - Tomura, M
AU  - Tomura M
FAU - Fujiwara, H
AU  - Fujiwara H
FAU - Kurimoto, M
AU  - Kurimoto M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-2)
RN  - 0 (Recombinant Proteins)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Drug Synergism
MH  - Female
MH  - Interferon-gamma/*biosynthesis
MH  - Interleukin-12/administration & dosage
MH  - Interleukin-18/*administration & dosage
MH  - Interleukin-2/*administration & dosage
MH  - Killer Cells, Natural/*drug effects/*immunology
MH  - Liver/cytology/drug effects/immunology
MH  - Lung Neoplasms/drug therapy/immunology/secondary
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Recombinant Proteins/administration & dosage
MH  - Spleen/cytology/drug effects/immunology
MH  - Tumor Cells, Cultured
EDAT- 2000/03/14 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/03/14 09:00
PHST- 2000/03/14 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/03/14 09:00 [entrez]
AID - 10.1089/107999000312630 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2000 Feb;20(2):217-24. doi: 10.1089/107999000312630.