The effects of chromium and copper supplementation on mitogen-stimulated T cell proliferation in hypercholesterolaemic postmenopausal women

Rhee, Yeong; Hermann, Janice; Burnham, Kim; Arquitt, Andrea; Stoecker, Barbara J.

doi:10.1046/j.1365-2249.2002.01697.x

Cited by 9 publications

(4 citation statements)

References 36 publications

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“…Another study demonstrated a copper requirement for the oligomerization of chemokines for inducing T‐cell migration (43). Lastly, lymphocytes collected from patients who had received 12 wk of Cu + and Cr + supplements showed decreased proliferation in response to in vitro stimulation compared to those from patients who had only received Cr + supplementation over that time period (44). The fact that we did not observe a defect in IL‐2 production associated with concentrations of Dp44mT necessary to inhibit T‐cell activation suggests that copper may simply mediate the drug's activity in this context.…”

Section: Discussionmentioning

confidence: 99%

The anticancer drug Dp44mT inhibits T‐cell activation and CD25 through a copper‐dependent mechanism

et al. 2012

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The di-2-pyridylketone thiosemicarbazone Dp44mT is a metal-chelating compound that has been demonstrated to have potent activity as an anticancer agent. Here we report that it also has a dramatic inhibitory effect on T-cell activation in vitro. We found that 10 nM Dp44mT (IC(50) 3.2 nM) prevented the up-regulation of surface CD25, and completely suppressed the activation and proliferation of splenic T cells isolated from Mus musculus that were stimulated with either T-cell receptor (TCR) cross-linking antibodies or phorbol ester plus ionomycin. In contrast, Dp44mT had no adverse effects on the survival of resting T cells. In addition, T cells stimulated in the presence of Dp44mT maintained the ability to up-regulate CD69 surface expression and secrete interleukin-2. Consistent with these observations, Dp44mT did not inhibit multiple canonical signals downstream of the TCR, including the nuclear factor of activated T cells. The effects of Dp44mT were easily mitigated by addition of nontoxic copper chelators or N-acetylcysteine, indicating a role for copper and reactive oxygen species in its actions. Together, these findings suggest that Dp44mT may serve as a potent immunosuppressive agent that could complicate its use as a cancer therapeutic agent, but might have utility in the treatment of autoimmunity.

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Section: Discussionmentioning

confidence: 99%

The anticancer drug Dp44mT inhibits T‐cell activation and CD25 through a copper‐dependent mechanism

et al. 2012

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“…Cr (III) does not only have roles in innate immune system but also in humoral one. Lymphocytic proliferation was found to decrease when copper was added to Cr supplementation in Rhee et al study (Rhee et al 2002 ). Another study found that antibody production decreased, spleen weight lessened, splenocytes number and percentage of blood lymphocytes were reduced in Oreochromis mossambicus fish when exposed to either trivalent or hexavalent Cr (Arunkumar et al 2000 ).…”

Section: Introductionmentioning

confidence: 97%

Trivalent chromium supplementation ameliorates adjuvant induced rheumatoid arthritis through up-regulation of FOXP3 and decrease in synovial Cathepsin G expression

et al. 2022

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Background Rheumatoid arthritis (RA) is a known debilitating autoimmune disease. Immune-suppressants that are used for disease treatment have serious side effects, therefore, trivalent chromium (Cr (III)); which has shown evidence of its influences on some inflammatory pathways and cytokines; was used in this study for the first time to be assessed for its therapeutic effect in RA rat model and was compared to prednisolone in a trial to find a treatment with lesser side effects. Methods Adult male albino rats were randomly divided into four groups: normal, untreated RA, prednisolone treated RA (1.25 mg/kg/day) and Cr (III) treated RA groups (80 μg/kg/day), induction of RA was done by subcutaneous complete Freund adjuvant injection. Study duration was 4 weeks throughout which arthritis scoring and weight measurement were pursued. Histopathological examination and immunohistochemical FOXP3 assessment were done for joint biopsies. Serum inflammatory markers (interleukin 17, interleukin 10, CRP) and synovial erosive arthritis marker (Cathepsin G) were measured. HDL and non-HDL cholesterol were estimated as well. Results Cr (III) treatment showed marked clinical and histopathological improvement, also astonishing anti-inflammatory effects (increase in FOXP3 expression and interleukin 10, with decrease in interleukin 17, CRP and synovial Cathepsin G) to the extent that Cr (III) effects on inflammation abolishment were comparable to that of prednisolone and even better at some aspects. Moreover, Cr (III) was protective from side effects, i.e., weight gain and dyslipidemia that were seen with prednisolone treatment. Conclusions Cr (III) is promising in treating RA and it lacks some side effects of accustomed immune-modulatory agents including prednisolone. Further experimental studies and clinical trials should be held to see the efficacy of Cr (III) in different doses and to assess its long term side effects when used for rheumatoid arthritis and other autoimmune diseases treatment.

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“…It has been reported that supplementation with Vitamin E, a potent antioxidant, and trace elements, such as Zinc (Zn), Selenium (Se), and Copper (Cu), improves the immune response. For example, Vitamin E increases lymphocyte proliferation in response to mitogens 25 ; Zn enhances phagocytic activity and antigen presentation to T-lymphocytes 26,27 ; Se and Cu increase T-cell differentiation and proliferative responses, superoxide dismutase, and IL-2 levels [28][29][30][31][32] . In view of these beneficial effects, it is relevant to evaluate the effect of such supplements to improve the immune system function after SCI.…”

Section: Introductionmentioning

confidence: 99%

Supplementation With Vitamin E, Zinc, Selenium, and Copper Re-Establishes T-Cell Function and Improves Motor Recovery in a Rat Model of Spinal Cord Injury

et al. 2022

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Spinal cord injury (SCI) causes a dysfunction of sympathetic nervous system innervation that affects the immune system, leading to immunosuppression syndrome (ISS) and contributing to patient degeneration and increased risk of several infections. A possible therapeutic strategy that could avoid further patient deterioration is the supplementation with Vitamin E or trace elements, such as Zinc, Selenium, and Copper, which individually promotes T-cell differentiation and proliferative responses. For this reason, the aim of the present study was to evaluate whether Vitamin E, Zinc, Selenium, and Copper supplementation preserves the number of T-lymphocytes and improves their proliferative function after traumatic SCI. Sprague–Dawley female rats were subjected to moderate SCI and then randomly allocated into three groups: (1) SCI + supplements; (2) SCI + vehicle (olive oil and phosphate-buffered saline); and (3) sham-operated rats. In all rats, the intervention was initiated 15 min after SCI and then administered daily until the end of study. Locomotor recovery was assessed at 7 and 15 days after SCI. At 15 days after supplementation, the quantification of the number of T-cells and its proliferation function were examined. Our results showed that the SCI + supplements group presented a significant improvement in motor recovery at 7 and 15 days after SCI. In addition, this group showed a better T-cell number and proliferation rate than that observed in the group with SCI + vehicle. Our findings suggest that Vitamin E, Zinc, Selenium, and Copper supplementation could be part of a therapy for patients suffering from acute SCI, helping to preserve T-cell function, avoiding complications, and promoting a better motor recovery. All procedures were approved by the Animal Bioethics and Welfare Committee (Approval No. 201870; CSNBTBIBAJ 090812960).

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The effects of chromium and copper supplementation on mitogen-stimulated T cell proliferation in hypercholesterolaemic postmenopausal women

Cited by 9 publications

References 36 publications

The anticancer drug Dp44mT inhibits T‐cell activation and CD25 through a copper‐dependent mechanism

The anticancer drug Dp44mT inhibits T‐cell activation and CD25 through a copper‐dependent mechanism

Trivalent chromium supplementation ameliorates adjuvant induced rheumatoid arthritis through up-regulation of FOXP3 and decrease in synovial Cathepsin G expression

Supplementation With Vitamin E, Zinc, Selenium, and Copper Re-Establishes T-Cell Function and Improves Motor Recovery in a Rat Model of Spinal Cord Injury

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