Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy.
In this study, we examined the effect of injecting various cytokines. We report here that tumour necrosis factor (TNF)alpha, gamma-interferon and interleukin 2 (IL-2) can, in some circumstances, increase fetal resorption rates in abortion-prone (CBA/J x DBA/2) and non-abortion prone (CBA/J x BALB/c,C3H x DBA/2) matings: 1000 units TNF enhanced resorptions from 43 to 79% in CBA x DBA/2, from 7 to 89% in CBA x BALB/c, from 5 to 47% in C3H x DBA/2. The effect was both gestational age- and dose-dependent. Gamma interferon and R-IL-2 enhanced resorptions from 38 to 68% and 76% respectively in the CBA/J x DBA/2 mating combination, whereas the rates in CBA/J x BALB/c matings were enhanced from 6 to 44% and 55%. Lipopolysaccharide (LPS), which is known to lead to the release of TNF-alpha, had a similar effect, leading to gestational age- and dose-dependent enhancement of resorptions up to 100%. However, cytokines of the CSF family, including IL-3 and GM-CSF, increased the chances of fetal survival when injected into abortion-prone mice, e.g. reducing resorption rates in the abortion-prone CBA/J x DBA/2 mating combination from 55 to 22% (IL-3), and 47 to 8% (GM-CSF). They also increased fetal and placental weight and, in particular, expanded the spongiotrophoblast zone in the placenta. The latter observations may be due to a direct trophic influence on placental cells, perhaps through a cytokine cascade, or an indirect effect due to inhibition of natural killer (NK)-like cells, or both. Whatever the mechanism, these results may find practical application in influencing reproductive outcome in women and other species.
Chaouat
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U 262 INSERM, Clinique Universitaire Baudelocque, Paris, France.
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D000818:Animals; D003115:Colony-Stimulating Factors / Q000627:therapeutic use; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D005327:Fetal Resorption / Q000139:chemically induced / Q000517:prevention & control*; D005333:Fetus / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use; D007371:Interferon-gamma / Q000009:adverse effects; D007376:Interleukin-2 / Q000009:adverse effects; D007377:Interleukin-3 / Q000627:therapeutic use; D008222:Lymphokines / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor