Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression

Apoptosis : an International Journal on Programmed Cell Death
Marianne MikkelsenKlaus Bendtzen

Abstract

Spironolactone (SPIR) has been described to suppress accumulation of pro-inflammatory cytokines. Here, the suppression of TNF-alpha in lipopolysaccharide (LPS)-stimulated mononuclear cell cultures was confirmed. However, SPIR was also found to induce apoptosis, prompting the investigations of a possible association between the two effects: The apoptosis-inducing and the cytokine-suppressive effects of SPIR correlated with regard to the effective concentration range. Also, pre-incubation experiments demonstrated a temporal separation of the two effects of < or = 4 h, with TNF-alpha suppression preceding apoptosis. An association between the two effects was also seen when testing several SPIR analogues. Contrary to TNF-alpha, the levels of IL-1beta increased in SPIR-treated cultures. However, the amount of IL-1beta in the supernatants depended upon the order of SPIR and LPS addition, as IL-1beta was non-detectable in cultures treated with SPIR prior to LPS, whereas elevated IL-1beta levels were seen when SPIR was added after LPS-stimulation. It is possible that the extracellular accumulation of IL-1beta is due to an increased release of already produced IL-1beta as a result of cell death. In conclusion, suppression of cytokine pr...Continue Reading

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Citations

Oct 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·Søren Ulrik Salling SønderKlaus Bendtzen
May 8, 2009·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Nadeem KhanNirmal Singh
Nov 30, 2007·Ophthalmic Research·Ljiljana OtasevicUwe Pleyer
Dec 12, 2012·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Ayelet Raz-PasteurShlomo Keidar

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis