Th1 cytokines and the prothrombinase fgl2 in stress-triggered and inflammatory abortion.
OBJECTIVE
The immune system contributes to the outcome of pregnancy by complex immunological interactions. Cytokines especially influence the immune milieu pro or contra pregnancy. T helper 1 (Th1) cytokines [tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] cause inflammation and together are thought to threaten the maintenance of pregnancy. It has been proposed that increased levels of these Th1 cytokines activate coagulation via up-regulating the novel prothrombinase, fgl2. This study further investigates the Th1 cytokine up-regulation of fgl2 expression in a pathophysiological, stress induced abortion model, and an inflammatory, interleukin-12 (IL-12) triggered abortion model.


METHODS
The DBA/2J-mated CBA/J female mice were exposed to sonic sound stress or were injected with IL-12 during early gestation. On day 13.5 of pregnancy the uteri were removed and the resorption rate was calculated. We evaluated TNF-alpha, IFN-gamma, fgl2 as well as IL-12 messenger RNA (mRNA) expression in decidual samples of all mice by quantitative, real-time polymerase chain reaction (PCR).


RESULTS
A similar resorption rate of 24% was detected in stressed mice, as well as in IL-12 injected mice compared with approximately 11% in non-stressed, non-injected control mice. In stressed mice compared with controls, we observed on day 13.5 up-regulated TNF-alpha, unchanged IFN-gamma down-regulated fgl2, and a slightly increased levels of IL-12. In the IL-12 triggered abortion model, we observed up-regulated levels of TNF-alpha, IFN-gamma and fgl2.


CONCLUSIONS
These novel data suggest two distinct cytokine patterns leading to similar abortion rates. A physiological cascade associated with up-regulation of TNF-alpha, and an IL-12-triggered cascade characterized by persistent up-regulation of TNF-alpha and IFN-gamma as well as a persistent increase in fgl2.
Knackstedt
M K
MK
Department of Internal Medicine, Charité, Charité, Humboldt University, Berlin, Germany.
Zenclussen
A C
AC
Hertwig
K
K
Hagen
E
E
Dudenhausen
J W
JW
Clark
D A
DA
Arck
P C
PC
D000022:Abortion, Spontaneous / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D005260:Female; D007249:Inflammation / Q000150:complications; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D023421:Models, Animal; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000150:complications; D013925:Thromboplastin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D013925:Thromboplastin