Th1 Cytokines and the Prothrombinase fgl2 in Stress‐triggered and Inflammatory Abortion Journal Articles uri icon

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abstract

  • PROBLEM:  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‐α (TNF‐α) and interferon‐γ (IFN‐γ)] 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.METHOD:  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‐α, IFN‐γ, 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‐α, unchanged IFN‐γ 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‐α, IFN‐γ and fgl2.CONCLUSION:  These novel data suggest two distinct cytokine patterns leading to similar abortion rates. A physiological cascade associated with up‐regulation of TNF‐α, and an IL‐12‐triggered cascade characterized by persistent up‐regulation of TNF‐α and IFN‐γ as well as a persistent increase in fgl2.

authors

publication date

  • April 2003