Changes in the Immune System of Female Wistar Rats After Exposure to Immunosuppressive Treatment During Pregnancy

Abstract

This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL-17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner.

Changes in the immune system in experimental acanthamoebiasis in immunocompetent and immunosuppressed hosts

“…Immunophenotypic analysis of splenocytes by flow cytometry was undertaken as described by Kabat-Koperska et al [ 19 ], and this test was only performed for immunosuppressed animals, including AS and CS groups. Spleens were collected during the section of the animals, then placed in Hank’s 1× balanced salt solutions, cut into pieces, pressed through nylon to sterile Roswell Park Memorial Institute medium (Sigma-Aldrich, St. Louis, USA ) containing phenol red and L-glutamine.…”

“…Cell suspensions at a density of 2 × 10 6 lymphocytes were placed in wells, 0.5 ml of cell suspension in 1 ml of incubation medium: RPMI, 10% bovine serum, 50 μg/ml of gentamycin and increasing amounts of concanavalin A (ConA, 0 μg/ml; 5 μg/ml) we estimated the functional response to this mitogen [ 19 ]. Incubation of lymphocytes in the well plates was carried out at 37 °C for 72 h under an atmosphere containing 5% CO 2 .…”

The Comparison of Parameters of Oxidative Stress in Native Rat Livers Between Different Immunosuppressive Regimens

“…to prolong the lifespan of the graft while avoiding or minimizing side effects. The mechanism of toxicity of immunosuppressive drugs is mostly associated with the generation of ROS and the induction of oxidative stress [17,[23][24][25][26][27]. Oxidative stress injures many organs, including the liver, which is an intensely metabolic organ whose physiology is very complex.…”

Proteomic study on the lymphocytes from pregnant Wistar rat females treated with immunosuppressive regimen

“…Our center previously performed experiments targeting the cytokine profiles of lymphocytes obtained from pregnant female Wistar rats and their offspring treated with different immunosuppressive regimens and further stimulated with concanavalin A (ConA) 17 . We have indicated several differences regarding the cytokines’ secretion.…”