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

Abstract

BackgroundIn 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.MethodsThe 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.ResultsThere 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.ConclusionQualitative, 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.

Comparison of effects of the tacrolimus and cyclosporine A on the colon anastomosis recovery of rats

“…New studies are needed to evaluate the effects of different dosages in different time spans. The drug dosages used were based on previous studies [ 7 8 ]. However, monitoring immunosuppressive activity may be useful in assessing toxicity and efficiency of drugs used in future studies.…”

“…The drug dosages were calculated according to data found in the cited literature [ 7 8 ]. While TAC is toxic in high doses, 0.1–10 mg/kg/day dosages of TAC have been administered for different purposes and its use reported in various studies.…”

Current Status Regarding Immunosuppressive Treatment in Patients after Renal Transplantation

“…Kabat-Koperska et al [ 47 ] indicated qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females. The thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen-dependent manner [ 47 ]. It should be also emphasised that CNIs disturb oxidative stress.…”

“…Wang et al [ 67 ] suggest that glycyrrihizic acid and prednisone improve renal function, relieve the renal morphological changes, and decrease interstitial fibrosis in rats [ 67 ]. However, some researchers, based on the examination of immunosuppressive regimens, where prednisone was included, indicated the severe effect of these drugs on various tissues, including kidney [ 46 , 47 , 52 ]. Nevertheless, these studies concerned triple-drug protocols; therefore, the role of prednisone on organs was not clear [ 46 , 47 , 52 ].…”

“…However, some researchers, based on the examination of immunosuppressive regimens, where prednisone was included, indicated the severe effect of these drugs on various tissues, including kidney [ 46 , 47 , 52 ]. Nevertheless, these studies concerned triple-drug protocols; therefore, the role of prednisone on organs was not clear [ 46 , 47 , 52 ]. Interestingly, treatment with daily prednisone compared with intermittent prednisone (alternating 10 days on and 10 days off) led to a significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and general satisfaction among patients with Duchenne muscular dystrophy [ 68 ].…”