The value of in vitro immune function tests in the detection of potential immunotoxicants

Crevel, R.W.R.; Buckley, Patrick J.; Robinson, J.A.

doi:10.1016/0887-2333(94)90237-2

Cited by 3 publications

(8 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only postnatal treatment of juvenile rodents with CsA has been reported to result in morphological and functional abnormalities of the thymus and spleen. 19 Other authors have observed a dose-dependent reduction in thymus weight only in adult male rats treated with CsA, 18 and CsA and MMF, 21 while the spleen remained unaffected.…”

Section: Discussionmentioning

confidence: 96%

“…Immunotoxicity can be defined as an adverse effect on the immune system that occurs at a dose that produces no general systemic toxic effects. 18 Exposure to immunosuppressive treatment during pregnancy can result in persistent impairment of the immune organs of both the mother and the fetus. 1 , 19 The fetus is often more sensitive to many toxic agents.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Kabat‐Koperska¹,

Kolasa²,

Wojciuk³

et al. 2016

DDDT

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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

Kabat‐Koperska¹,

Kolasa²,

Wojciuk³

et al. 2016

DDDT

View full text Add to dashboard Cite

show abstract

“…Most of studies focused on immunotoxicity were carried out generally on male rats [15,18]. In our experimental study, we assessed the impact of immunosuppressive drugs on changes in the immune system in female Wistar rats during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Eight rats did not receive treatment, as they formed a control group and were given the vehicle and olive oil under identical conditions as other used in experiment rats. The drug doses were based on data available in the literature [6][7][8][9][10][11][12][13][14][15]. A diagram of the study is presented in Table 1.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

“…However, we do not deny the usefulness of immunofunctional assays to evaluate immunotoxicity, because there are many procedures (Vos and van Loveren, 1987;Luster et al, 1988;Verdier, 1992) and techniques (Miller, 1992;Fautz and Miltenburger, 1993;Crevel et al, 1994;Meredith and Miller, 1994;Lebrec et al, 1995) other than the PFC assay, including host resistance assays (Luster et al, 1993), which can provide valuable information about the possible mechanisms involved in chemical-induced immune dysfunction and the ability to resist infection and cancer.…”

Section: Figmentioning

confidence: 97%

Dose–Response Relationships of Weight, Cellularity, Plaque-Forming Cell Response, and Histology in the Spleen of Rats Treated with Antimetabolites

Doi

Nagai

Tsukuda

et al. 1996

Journal of the American College of Toxicology

View full text Add to dashboard Cite

Our previous reports revealed the usefulness of investigating the changes in the weight, cellularity, and histology in the spleen caused by alkylating agents to evaluate immunotoxicity, compared with the plaque-forming cell (PFC) assay using appropriate conditions. In this study, dose-response relationships of weight, cellularity, PFC response, and histology in the spleen in rats treated with antimetabolites were studied. A single administration of azathioprine or 6-mercaptopurine (6-MP) caused decreases in spleen weights and cellularity and the PFC response at nearly the same dose level. In the rats treated with these agents for 7 days, spleen weights and cellularity tended to be decreased at doses lower than those suppressing the PFC response. In the rats singly treated with 5-fluorouracil (5-FU), spleen weights and cellularity were decreased at a dose lower than that suppressing the PFC response. At low and middle doses, the PFC response was inversely enhanced by this agent. A 7-day administration of 5-FU caused reductions in spleen weights and cellularity and PFC response at the same dose level. In addition, the spleen in the rats dosed with azathioprine, 6-MP, or 5-FU was histopathologically examined and indicated a dose-related decrease in the size of the spleen without changes in the tissue architecture at doses suppressing the PFC response. On the other hand, in the red pulp, the extramedullary hematopoiesis disappeared by these antimetabolites at the doses. These results indicate that decreases in the weight and cellularity and histological changes in the spleen caused by antimetabolites are detectable at doses suppressing the PFC response. Key Words: Immunotoxicity-Fischer 344 rats-Spleen-Azathioprine-6-Mercaptopurine-5-Fluorouracil.Chemically induced immunotoxicity continues to play an important role in the safety and risk assessment process (Vos

show abstract

The value of in vitro immune function tests in the detection of potential immunotoxicants

Cited by 3 publications

References 6 publications

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

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

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

Dose–Response Relationships of Weight, Cellularity, Plaque-Forming Cell Response, and Histology in the Spleen of Rats Treated with Antimetabolites

Contact Info

Product

Resources

About