|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 August 2000, Vol. 96, No. 4, pp. 1465-1473
IMMUNOBIOLOGY
Coadministration of interleukin-18 and interleukin-12 induces a
fatal inflammatory response in mice: critical role of natural killer
cell interferon- production and STAT-mediated signal
transduction
William E. Carson,
Julie E. Dierksheide,
Saad Jabbour,
Mirela Anghelina,
Page Bouchard,
George Ku,
Haixin Yu,
Heinz Baumann,
Manisha H. Shah,
Megan A. Cooper,
Joan Durbin, and
Michael A. Caligiuri
From the Departments of Pathology, Medicine, and
Surgery, Arthur G. James Comprehensive Cancer Center, The Ohio State
University, Columbus, OH; Children's Hospital, Columbus, OH; Vertex
Pharmaceuticals, Cambridge, MA; Genetics Institute, Andover, MA; and
Roswell Park Cancer Institute, Buffalo, NY.
The administration of therapeutic doses of recombinant cytokines to
patients with malignant disease can be complicated by systemic
toxicities, which in their most severe form may present as a systemic
inflammatory response. The combination of interleukin (IL)-18 and
IL-12 has synergistic antitumor activity in vivo yet has been
associated with significant toxicity. The effects of IL-18 plus IL-12
were examined in a murine model, and it was found that the daily,
simultaneous administration of IL-18 and IL-12 resulted in systemic
inflammation and 100% mortality within 4 to 8 days depending on the
strain employed. Mice treated with IL-18 plus IL-12 exhibited unique
pathologic findings as well as elevated serum levels of proinflammatory
cytokines and acute-phase reactants. The actions of tumor necrosis
factor- did not contribute to the observed toxicity, nor did T or B
cells. However, toxicity and death from treatment with IL-18 plus IL-12
could be completely abrogated by elimination of natural killer (NK)
cells or macrophages. Subsequent studies in genetically altered mice
revealed that NK-cell interferon- mediated the fatal toxicity via
the signal transducer and activator of transcription pathway of
signal transduction. These data may provide insights into methods of
ameliorating cytokine-induced shock in humans.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. C. Rodriguez-Galan, D. Reynolds, S. G. Correa, P. Iribarren, M. Watanabe, and H. A. Young
Coexpression of IL-18 Strongly Attenuates IL-12-Induced Systemic Toxicity through a Rapid Induction of IL-10 without Affecting its Antitumor Capacity
J. Immunol.,
July 1, 2009;
183(1):
740 - 748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Gross, C. Grupp, C. Steinberg, S. Zimmermann, D. Strasser, N. Hannesschlager, W. Reindl, H. Jonsson, H. Huo, D. R. Littman, et al.
Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-{kappa}B and MAPK activation to selectively control cytokine production
Blood,
September 15, 2008;
112(6):
2421 - 2428.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Sennello, R. Fayad, M. Pini, M. E. Gove, V. Ponemone, R. J. Cabay, B. Siegmund, C. A. Dinarello, and G. Fantuzzi
Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice
PNAS,
June 10, 2008;
105(23):
8085 - 8090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Cooley, F. Xiao, M. Pitt, M. Gleason, V. McCullar, T. L. Bergemann, K. L. McQueen, L. A. Guethlein, P. Parham, and J. S. Miller
A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature
Blood,
July 15, 2007;
110(2):
578 - 586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Subleski, V. L. Hall, T. C. Back, J. R. Ortaldo, and R. H. Wiltrout
Enhanced Antitumor Response by Divergent Modulation of Natural Killer and Natural Killer T Cells in the Liver.
Cancer Res.,
November 15, 2006;
66(22):
11005 - 11012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. MacGregor, Q. Li, A. E. Chang, T. M. Braun, D. P.M. Hughes, and K. T. McDonagh
Ex vivo Culture with Interleukin (IL)-12 Improves CD8+ T-Cell Adoptive Immunotherapy for Murine Leukemia Independent of IL-18 or IFN-{gamma} but Requires Perforin.
Cancer Res.,
May 1, 2006;
66(9):
4913 - 4921.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Cooley, V. McCullar, R. Wangen, T. L. Bergemann, S. Spellman, D. J. Weisdorf, and J. S. Miller
KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation
Blood,
December 15, 2005;
106(13):
4370 - 4376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Eisenbeis, G. B. Lesinski, M. Anghelina, R. Parihar, D. Valentino, J. Liu, P. Nadella, P. Sundaram, D. C. Young, M. Sznol, et al.
Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12
J. Clin. Oncol.,
December 1, 2005;
23(34):
8835 - 8844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Roda, R. Parihar, and W. E. Carson III
CpG-Containing Oligodeoxynucleotides Act through TLR9 to Enhance the NK Cell Cytokine Response to Antibody-Coated Tumor Cells
J. Immunol.,
August 1, 2005;
175(3):
1619 - 1627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Woldbaek, J. B. Sande, T. A. Stromme, P. K. Lunde, S. Djurovic, T. Lyberg, G. Christensen, and T. Tonnessen
Daily administration of interleukin-18 causes myocardial dysfunction in healthy mice
Am J Physiol Heart Circ Physiol,
August 1, 2005;
289(2):
H708 - H714.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mavropoulos, G. Sully, A. P. Cope, and A. R. Clark
Stabilization of IFN-{gamma} mRNA by MAPK p38 in IL-12- and IL-18-stimulated human NK cells
Blood,
January 1, 2005;
105(1):
282 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ishida, T. Maegawa, T. Kondo, A. Kimura, Y. Iwakura, S. Nakamura, and N. Mukaida
Essential Involvement of IFN-{gamma} in Clostridium difficile Toxin A-Induced Enteritis
J. Immunol.,
March 1, 2004;
172(5):
3018 - 3025.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Leung, R. Iyengar, V. Turner, P. Lang, P. Bader, P. Conn, D. Niethammer, and R. Handgretinger
Determinants of Antileukemia Effects of Allogeneic NK Cells
J. Immunol.,
January 1, 2004;
172(1):
644 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Yu, C. S. Tripp, and J. H. Russell
Regulation and Phenotype of an Innate Th1 Cell: Role of Cytokines and the p38 Kinase Pathway
J. Immunol.,
December 1, 2003;
171(11):
6112 - 6118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Fantuzzi, N. K. Banda, C. Guthridge, A. Vondracek, S.-H. Kim, B. Siegmund, T. Azam, J. A. Sennello, C. A. Dinarello, and W. P. Arend
Generation and characterization of mice transgenic for human IL-18-binding protein isoform a
J. Leukoc. Biol.,
November 1, 2003;
74(5):
889 - 896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Reddy, T. Teshima, G. Hildebrandt, D. L. Williams, C. Liu, K. R. Cooke, and J. L.M. Ferrara
Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects
Blood,
April 1, 2003;
101(7):
2877 - 2885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Okamoto, S. Kato, K. Oizumi, M. Kinoshita, Y. Inoue, K. Hoshino, S. Akira, A. N. J. Mckenzie, H. A. Young, and T. Hoshino
Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia
Blood,
February 15, 2002;
99(4):
1289 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Whitman, P. Ravisankar, and A. Daugherty
Interleukin-18 Enhances Atherosclerosis in Apolipoprotein E-/- Mice Through Release of Interferon-{gamma}
Circ. Res.,
February 8, 2002;
90
(2):
e34 - e38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Reddy, T. Teshima, M. Kukuruga, R. Ordemann, C. Liu, K. Lowler, and J. L.M. Ferrara
Interleukin-18 Regulates Acute Graft-Versus-Host Disease by Enhancing Fas-mediated Donor T Cell Apoptosis
J. Exp. Med.,
November 12, 2001;
194(10):
1433 - 1440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Godshall, A. B. Lentsch, J. C. Peyton, M. J. Scott, and W. G. Cheadle
STAT4 Is Required for Antibacterial Defense but Enhances Mortality during Polymicrobial Sepsis
Clin. Vaccine Immunol.,
November 1, 2001;
8(6):
1044 - 1048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Mordue, F. Monroy, M. La Regina, C. A. Dinarello, and L. D. Sibley
Acute Toxoplasmosis Leads to Lethal Overproduction of Th1 Cytokines
J. Immunol.,
October 15, 2001;
167(8):
4574 - 4584.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Whitman, P. Ravisankar, and A. Daugherty
Interleukin-18 Enhances Atherosclerosis in Apolipoprotein E-/- Mice Through Release of Interferon-{gamma}
Circ. Res.,
February 8, 2002;
90
(2):
e34 - e38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
