Modulation of human peripheral blood mononuclear cell proliferative response by diltiazem: in vitro comparison in younger versus older subjects.
BACKGROUND: The gradual aging of population has increased the number of elderly patients receiving kidney transplants. In elderly transplant recipients, careful immunosuppression has to be maintained to avoid both rejection and adverse effects. Clinical protocols after kidney transplantation include...
| Publicado en: | Drugs & Aging Vol. 26; no. 1; pp. 87 - 95 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105630319&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105630319 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 1170229X C5B jtl: Drugs & Aging issn: 1170229X maglogo: N pubinfo: dt: 2009 vid: 26 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105630319 105630319 2010170641 10.2165/0002512-200926010-00007 NLM19102517 105630319 ppf: 87 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Modulation of human peripheral blood mononuclear cell proliferative response by diltiazem: in vitro comparison in younger versus older subjects. aug: au: D'Ambrosio A Giordani L Colucci M Vanacore N Quintieri F affil: Department of Infectious, Parasitic and Immuno-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy. sug: subj: Cyclosporine Adverse Effects Diltiazem Therapeutic Use Immunosuppression Methods Lymphocytes Adult Aged Female In Vitro Studies Male Middle Age Pearson's Correlation Coefficient Research Methodology T-Tests Human Adult: 19-44 years Aged: 65+ years Middle Aged: 45-64 years Female Male ab: BACKGROUND: The gradual aging of population has increased the number of elderly patients receiving kidney transplants. In elderly transplant recipients, careful immunosuppression has to be maintained to avoid both rejection and adverse effects. Clinical protocols after kidney transplantation include use of the calcium channel antagonist diltiazem to ameliorate the hypertensive effect and nephrotoxicity of the immunosuppressant agent ciclosporin (cyclosporine). OBJECTIVE: Since immune response can be impaired by senescence, we evaluated the influence of diltiazem on lymphocyte proliferation both alone and in the presence of ciclosporin in younger versus older subjects. METHODS: Peripheral blood mononuclear cells (PBMC) from younger healthy donors (aged 19-24 years) and older subjects (aged 59-65 years) were isolated and stimulated with mitogens, recombinant human interleukin-2 (IL-2), purified protein derivative (PPD) antigen from Mycobacteriumtuberculosis, and anti-CD3 monoclonal antibody (alphaCD3 moAb) in the presence or absence of 10(-4), 10(-5), 10(-6), 10(-7) mol/L concentrations of diltiazem. In some experiments, lymphocytes from younger and older subjects were used as responder cells in an allogeneic mixed lymphocyte reaction (MLR) in the presence of different concentrations of diltiazem and 10 ng/mL of ciclosporin. RESULTS: We found that PBMC from older subjects were more susceptible to immunosuppression induced by low concentrations of diltiazem when mitogens were used to stimulate cells. In particular, when pokeweed mitogen was used, diltiazem 10(-7) mol/L was associated with statistically significant immunosuppression in older subjects compared with younger subjects. This effect was not observed when IL-2, PPD antigen and alphaCD3 moAb were used as stimulators. Moreover, in the allogeneic MLR, we found no differences between younger and older subjects when the 10(-)(5), 10(-)(6) and 10(-7) mol/L concentrations of diltiazem were used alone or in the presence of ciclosporin. Only addition of the supratherapeutic 10(-4) mol/L concentration of diltiazem to ciclosporin was associated with statistically significant immunosuppression in older versus younger subjects. DISCUSSION: Our results show that PBMC from older subjects are no more susceptible than PBMC from younger subjects to therapeutic doses of diltiazem when T-cell receptors are directly or indirectly involved. On the contrary, when PBMC activation was not mediated by T-cell receptor involvement, as in the case of pokeweed mitogen, susceptibility to a therapeutic concentration of diltiazem in older subjects was enhanced. Moreover, co-administration of therapeutic doses of diltiazem and ciclosporin in an MLR showed no significant differences between younger and older subjects in an in vitro model of lymphocyte response to allogeneic transplantation. CONCLUSION: Since we found no variations in immunosuppression between older and younger subjects when therapeutic doses of diltiazem were added to ciclosporin, our data do not discourage the use of diltiazem in older kidney transplant recipients receiving ciclosporin therapy. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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