Effect of Different Immunosuppressive Drugs on Immune Cells from Young and Old Healthy Persons

Abstract

Background: Life expectancy, as well as the average age of patients undergoing solid organ transplantation, increases constantly. Consequently, immunosuppressive therapy is no longer limited to young organ recipients. Objective: Here, we investigate how different types of immunosuppressive therapy, namely the calcineurin inhibitors cyclosporin A and tacrolimus, as well as the mTOR inhibitor rapamycin, affect the function of immune cells in young and elderly persons. Methods: Proliferation, cell viability, cytokine production (IL-2, IFN-γ), H₂O₂ production and telomere length of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMCs) of young (n = 13; median age 27 years) and old (n = 19; median age 71 years) healthy donors were analyzed. Results: The inhibition of proliferation was dampened in PBMCs from elderly donors, especially after incubation with rapamycin. All three immunosuppressive drugs inhibited the production of IL-2 equally well, whereas the production of IFN-γ was less well inhibited by rapamycin. Both calcineurin inhibitors increased H₂O₂ concentrations after stimulation with PHA and led to a shortening of telomeres in PBMCs from young and old individuals. Rapamycin had only minor effects on H₂O₂ production and telomere length. Conclusion: Our results demonstrate that the effects of immunosuppressive drugs on PBMCs differ between young and elderly persons. Calcineurin inhibitors compared to rapamycin have a more pronounced prosenescence effect. These data indicate that specific treatment regimens for the elderly might therefore be considered.

Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

“…TL over time was similar in our 2 GVHD prophylaxis groups. To our knowledge, similar assessments have not been published previously; However, a relevant study of the effect of different immunosuppressive drugs on lymphocyte TL in healthy individuals was published by Welzl et al in 2014 [45]. Their in vitro results showed that CsA and Tac had a more pronounced prosenescence effect compared with rapamycin after short-term immunosuppressive treatment, with significantly less reduction of TL in peripheral blood mononuclear cells cultured in the presence of rapamycin.…”

Uremia-associated immunological aging is stably imprinted in the T-cell system and not reversed by kidney transplantation

“…The question remains why immunological aging does not reverse even when adequate graft function is achieved post‐KTx. As stated above, we cannot formally rule out that IS drugs prevent the restoration of thymic output, telomere length and reversal of memory T‐cell differentiation status . However, a more likely explanation might lie at the epigenetic level.…”

Perioperative Blood Transfusion, Age at Surgery, and Prognosis in a Database of 526 Upper Gastrointestinal Cancers

“…This finding suggests that the immune systems of young and older patients differ. Certainly, differences between immune systems of young and older animals have been demonstrated [17,39,40] . Book et al [17] have shown that older animals have significantly weaker responses to new alloantigen stimulation than young animals.…”