The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats

• Published in: Drug design, development and therapy development and therapy, 2016-07, Vol.2016 (Issue 1), p.2279-2288
• Main Authors: Kabat-Koperska J, Kolasa-Wołosiuk A, Wojciuk B, Wojciechowska-Koszko I, Roszkowska P, Krasnodębska-Szponder B, Paczkowska E, Safranow K, Gołembiewska E, Machaliński B, Ciechanowski K
• Format: Article
• Language: English
• Subjects: immune system; immunosuppressive drugs; kidney transplantation; pregnancy; Wistar rats
• ISSN: 1177-8881; 1177-8881

Joanna Kabat-Koperska,1 Agnieszka Kolasa-Wołosiuk,2 Bartosz Wojciuk,3 Iwona Wojciechowska-Koszko,3 Paulina Roszkowska,3 Barbara Krasnodębska-Szponder,3 Edyta Paczkowska,4 Krzysztof Safranow,5 Edyta Gołembiewska,1 Bogusław Machaliński,4 Kazimierz Ciechanowski1 1Department of Nephrology, Transplantology and Internal Medicine, 2Department of Histology and Embryology, 3Department of Microbiology and Immunological Diagnostics, 4Department of General Pathology, 5Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland Background: In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system - the thymus and the spleen. Methods: The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results: There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Conclusion: Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen-dependent manner. Keywords: immune system, immunosuppressive drugs, kidney transplantation, pregnancy, Wistar rats