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
References
Mar 1, 1992·Cytokine·M SvensonK Bendtzen
Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·K A HogquistD D Chaplin
Mar 1, 1990·Trends in Biochemical Sciences·A MueschT A Rapoport
May 12, 1989·Journal of Immunological Methods·M B HansenK Berg
Apr 1, 1989·Journal of Clinical Pharmacology·P GardinerA Karim
Jun 1, 1996·Journal of Pharmaceutical and Biomedical Analysis·A JankowskiH Lamparczyk
Jan 7, 2000·Cytokine·L S AndersenK Bendtzen
Apr 27, 2001·Expert Opinion on Investigational Drugs·S A Doggrell, L Brown
Jan 5, 2002·Apoptosis : an International Journal on Programmed Cell Death·K OkamotoH Kobayashi
Mar 20, 2002·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·O JónasdóttirK Bendtzen
Jul 3, 2003·Cell·Kodi S Ravichandran
Sep 17, 2003·Clinical and Experimental Immunology·K BendtzenUNKNOWN Spironolactone/Arthritis Study Group
Sep 23, 2003·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Ingrid Böhm, Hans Schild
Dec 4, 2003·Apoptosis : an International Journal on Programmed Cell Death·R OverbeekeC Haanen
Mar 17, 2004·Immunology Letters·Peter Riis HansenKlaus Bendtzen
Jul 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mark D Wewers
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
May 24, 2014·Immunopharmacology and Immunotoxicology·Yoshiro KatoTakashi Yokochi
Dec 12, 2012·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Ayelet Raz-PasteurShlomo Keidar
Jan 23, 2021·Pharmaceuticals·Katarzyna KotfisMiłosz Parczewski