T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells

J Immunol. 1996 Jan 15;156(2):653-62.

Abstract

Maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a Th1 response, whereas a Th2 response exacerbates the disease. We therefore asked whether the curative Th1 response against Leishmania major in genetically resistant C57BL/6 mice, would compromise concurrent pregnancy. The number of resorptions as assessed by uterine scars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 cytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57BL/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short period early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced higher resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only placental maintenance but also preimplantation events.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Susceptibility / immunology
  • Embryo Implantation*
  • Female
  • Fetal Resorption / etiology*
  • Genetic Predisposition to Disease
  • Interferon-gamma / metabolism*
  • Interleukin-10 / metabolism*
  • Interleukin-2 / metabolism
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL / immunology
  • Mice, Inbred C57BL / parasitology*
  • Placenta / immunology
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Complications, Parasitic / immunology*
  • Pregnancy Outcome
  • Species Specificity
  • Specific Pathogen-Free Organisms
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma