Clinical and experimental immunology
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Clin. Exp. Immunol. · Apr 2006
Randomized Controlled TrialShort-term simvastatin treatment has no effect on plasma cytokine response in a human in vivo model of low-grade inflammation.
Statins reduce plasma cholesterol, but clinical trials and in vitro studies indicate that they might also possess anti-inflammatory properties. The effect of simvastatin on circulating cytokines and leucocytes was evaluated in a human in vivo model of low-grade inflammation. Thirty young healthy male participants received an injection of the bacterial cell wall product endotoxin (0.06 ng/kg) to induce systemic inflammation. ⋯ Plasma cytokines as well as total leucocyte counts increased in all participants upon endotoxin challenge but were not affected by simvastatin treatment. Tolerance to endotoxin was observed in both groups after 14 days. Short-term treatment with simvastatin (20 mg/day) did not influence circulating cytokine levels during endotoxaemia in this human in vivo study.
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Clin. Exp. Immunol. · Apr 2006
A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis.
Active tuberculosis (TB) is associated with prolonged suppression of Mycobacterium tuberculosis (MTB)-specific immune responses, but mechanisms involved are understood incompletely. We investigated a potential role for CD4+CD25+ regulatory T cells in depressed anti-MTB immunity by evaluating serially CD4 cell phenotype and interferon (IFN)-gamma production by mononuclear cells from patients with TB. At diagnosis, frequencies of CD4+CD25+ T cells were increased in blood from TB patients compared to healthy purified protein derivative (PPD)-positive controls (with a history of prior TB exposure), and remained elevated at completion of therapy (6 months). ⋯ A role for CD4+CD25+ T cells in depressed IFN-gamma production during TB was substantiated in depletion experiments, where CD25+-depleted CD4 T cells produced increased amounts of IFN-gamma upon MTB stimulation compared to unseparated T cells. At follow-up, IFN-gamma production improved most significantly in blood from TB patients with high baseline frequencies of CD4+CD25+ T cells (more than threefold higher than controls for both total and CD25hi+ CD4 T cells), who also had a significant drop in frequencies of both total and 'regulatory' CD4+CD25+ T cells in response to treatment. Expansion of CD4+CD25+ regulatory T cells during active TB may play a role in depressed T cell IFN-gamma production.