| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*
Diabetes Research Institute, Heinrich-Heine University, Düsseldorf, Germany;
Institute of Diabetes Research, Munich, Germany;
Department of Endocrinology, Katholieke University, Leuven, Belgium;
Hyogo College of Medicine, Fujisaka, Japan; and
¶
Fujisaki Institute, Fujisaki, Japan
The development of type 1 diabetes in animal models is T cell and
macrophage dependent. Islet inflammation begins as peripheral benign
Th2 type insulitis and progresses to destructive Th1 type insulitis,
which is driven by the innate immune system via secretion of IL-12 and
IL-18. We now report that daily application of IL-18 to diabetes-prone
female nonobese diabetic mice, starting at 10 wk of age, suppresses
diabetes development (p < 0.001, 65% in
sham-treated animals vs 33% in IL-18-treated animals by 140 days of
age). In IL-18-treated animals, we detected significantly lower
intraislet infiltration (p < 0.05) and
concomitantly an impaired progression from Th2 insulitis to
Th1-dependent insulitis, as evidenced from IFN-
and IL-10 mRNA
levels in tissue. The deficient progression was probably due to lesser
mRNA expression of the Th1 driving cytokines IL-12 and IL-18 by the
innate immune system (p < 0.05). Furthermore, the
mRNA expression of inducible NO synthase, a marker of destructive
insulitis, was also not up-regulated in the IL-18-treated group. IL-18
did not exert its effect at the levels of islet cells. Cultivation of
islets with IL-18 affected NO production or mitochondrial activity and
did not protect from the toxicity mediated by IL-1
, TNF-
, and
IFN-. In conclusion, we show for the first time that administration
of IL-18, a mediator of the innate immune system, suppresses autoimmune
diabetes in nonobese diabetic mice by targeting the Th1/Th2 balance of
inflammatory immune reactivity in the pancreas.
This article has been cited by other articles:
|
|
 |
|
  T. Skurk, H. Kolb, S. Muller-Scholze, K. Rohrig, H. Hauner, and C. Herder The proatherogenic cytokine interleukin-18 is secreted by human adipocytes Eur. J. Endocrinol., June 1, 2005; 152(6): 863 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Johansson, H. Hall, J. Bjorklund, and P. Hoglund Broadly impaired NK cell function in non-obese diabetic mice is partially restored by NK cell activation in vivo and by IL-12/IL-18 in vitro Int. Immunol., January 1, 2004; 16(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. Schott, B. D. Haskell, H. M. Tse, M. J. Milton, J. D. Piganelli, C. M. Choisy-Rossi, P. C. Reifsnyder, A. V. Chervonsky, and E. H. Leiter Caspase-1 Is Not Required for Type 1 Diabetes in the NOD Mouse Diabetes, January 1, 2004; 53(1): 99 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Oikawa, A. Shimada, A. Kasuga, J. Morimoto, T. Osaki, H. Tahara, T. Miyazaki, F. Tashiro, E. Yamato, J.-i. Miyazaki, et al. Systemic Administration of IL-18 Promotes Diabetes Development in Young Nonobese Diabetic Mice J. Immunol., December 1, 2003; 171(11): 5865 - 5875. [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]
|
|
|
|
|
|
J. A. Gracie, S. E. Robertson, and I. B. McInnes Interleukin-18 J. Leukoc. Biol., February 1, 2003; 73(2): 213 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kretowski, K. Mironczuk, A. Karpinska, U. Bojaryn, M. Kinalski, Z. Puchalski, and I. Kinalska Interleukin-18 Promoter Polymorphisms in Type 1 Diabetes Diabetes, November 1, 2002; 51(11): 3347 - 3349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Leite-de-Moraes, A. Hameg, M. Pacilio, Y. Koezuka, M. Taniguchi, L. Van Kaer, E. Schneider, M. Dy, and A. Herbelin IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells J. Immunol., January 15, 2001; 166(2): 945 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Pauza, A. Nguyen, T. Wolfe, I-C. Ho, L. H. Glimcher, M. von Herrath, and D. Lo Variable Effects of Transgenic c-Maf on Autoimmune Diabetes Diabetes, January 1, 2001; 50(1): 39 - 46. [Abstract] [Full Text]
|
|
|
|
|
|
X.-q. Wei, B. P. Leung, H. M. L. Arthur, I. B. McInnes, and F. Y. Liew Reduced Incidence and Severity of Collagen-Induced Arthritis in Mice Lacking IL-18 J. Immunol., January 1, 2001; 166(1): 517 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Quintana, A. Rotem, P. Carmi, and I. R. Cohen Vaccination with Empty Plasmid DNA or CpG Oligonucleotide Inhibits Diabetes in Nonobese Diabetic Mice: Modulation of Spontaneous 60-kDa Heat Shock Protein Autoimmunity J. Immunol., December 1, 2000; 165(11): 6148 - 6155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Leung, I. B. McInnes, E. Esfandiari, X.-Q. Wei, and F. Y. Liew Combined Effects of IL-12 and IL-18 on the Induction of Collagen-Induced Arthritis J. Immunol., June 15, 2000; 164(12): 6495 - 6502. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
