Immune Reproductive Failure: Effect of Nonspecific Immunostimulation in Mouse Model

Abstract

There is much evidence that pregnancy loss may be immunologically mediated. Failure of the maternal immune system to actively support the pregnancy may be responsible for its demise. Potentiation of immune functions has been attempted in humans; however, the success of immunotherapy is still not clear. Thus immunotherapy experiments in mouse models are important. Nonspecific immuno-stimulation with complete Freund adjuvant (CFA) was shown in our laboratory to reverse the tendency to fetal loss in the CBA/J X DBA/2J mouse combination. CFA elevates the non-T lymphocyte population, decreases T-cell secreted lymphokines, and enhances macrophage-secreted monokines. However, a relationship between these changes and a beneficial effect of CFA on reproductive performance has to be proved. Information obtained from nonspecific immunopotentiation in the CBA/J-DBA/2J model may contribute the assessment of nonspecific immunotherapy in humans.

Ciprofloxacin Affects Pregnancy Loss in CBA/JxDBA/2J Mice Possibly via Elevation of Interleukin‐3 and Granulocyte Macrophage‐Colony Stimulating Factor Production

“…Immunization of women suffering from recurrent pregnancy loss by diverse means such as paternal or third party leukocytes or immunoglobulins was found to be successful in preventing fetal demise. 3,10,11 Similar results were obtained in the resorption-prone CBA/JxDBA/2J mouse model, which mimics human fetal loss, where immunization with paternal or third party leukocytes carrying the pater-nal MHC haplotype resulted in a decreased resorption rate. 1,12 -14 Also, nonspecific immunomodulation with CFA was shown by us to decrease fetal loss in the CBA/JxDBA/2J model, an effect that was associated with an increased number of Mac-1-positive cells in the spleen and placenta and an increased production of IL-1.…”

“…1,12 -14 Also, nonspecific immunomodulation with CFA was shown by us to decrease fetal loss in the CBA/JxDBA/2J model, an effect that was associated with an increased number of Mac-1-positive cells in the spleen and placenta and an increased production of IL-1. 15,3 In parallel, it was shown in several mouse models of pregnancy loss that various cytokines are capable of controlling fetal survival by decreasing the resorption rate and supporting placental growth and function. [16][17][18] This data concer with the well established role of various cytokines (especially CSFs), in supporting placental growth and fetal survival.…”

“…This mating combination exhibits an unusually high resorption rate (in the range of 30%), that occurs early in pregnancy and is accompanied by specific changes in the maternal immune profile. 1,3 Ciprofloxacin treatment resulted in a significant reduction in fetal loss as compared to treatment with the control antibiotic cetazidime or to non-treated animals. This effect of ciprofloxacin was found to be similar to that observed in mice with experimental APS.…”

“…It is believed that apart from anatomical and chromosomal embryonic defects, failure of the maternal immune system to actively support pregnancy, for example by production of the appropriate cytokine network, may be responsible for its demise. 1,2 Thus, immunotherapy procedures have been developed in which modulation of the maternal immune system by mononuclear blood cells of paternal origin, 1,3 non specific immunomodulators like Complete Freund Adjuvant (CFA) 3,4 or various cytokines, 2,4 decreased pregnancy loss in women suffering from habitual abortions 3 or in the resorption-prone CBA/JxDBA/2J mouse model. 1,2,4 Ciprofloxacin is a potent broad-spectrum antibacterial agent of the quinolone family, shown to affect various immune responses in humans and mice.…”

Diabetes teratogenicity is accompanied by alterations in macrophages and T cell subpopulations in the uterus and lymphoid organs

“…A similar normalizing effect of maternal immunopotentiation on the expression of all markers tested was demonstrated also in paraaortic lymph nodes. The immunopotentiationassociated normalization of Mac-1 expression in the uterus in the later stages of pregnancy was also demonstrated in our previous study following immunopotentiation with CFA, which was accompanied by a decreased resorption rate in the resorption-prone CBA/JXDBA/2J mouse combination [10]. In addition, the present data concur with our previous studies, demonstrating an immunopotentiation-associated improvement in reproductive performance, which was accompanied by normalization of TNFa and TGF-h2 expression in various models of teratogenic activity [17,18,23,24] or pregnancy loss [25].…”