title: Spironolactone inhibits production of proinflammatory cytokines by human mononuclear cells.
abstract: BACKGROUND
  The mineralocorticoid receptor antagonist spironolactone (SPIR) reduces the mortality and morbidity in patients with congestive heart failure (CHF). Overexpression of proinflammatory cytokines contribute to the development and progression of CHF.
  
  
  METHODS
  We examined the effect of SPIR on in vitro cytokine production by human peripheral blood mononuclear cells (PBMC). PBMC were cultured with 10-1000 microM SPIR and stimulated with lipopolysaccharide or phytohaemagglutinin-P. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-1beta, and interferon (IFN)-gamma were measured in culture supernatants by enzyme-linked immunosorbent assay and mRNA expression of the cytokines was determined by real-time reverse transcriptase polymerase chain reaction (PCR).
  
  
  RESULTS
  SPIR inhibited the stimulated production of TNF-alpha, IL-6, and IFN-gamma, whereas the release of IL-1beta was not significantly affected. The SPIR-induced cytokine inhibition occurred at the transcriptional level and was independent of antimineralocorticoid and antiandrogen activities.
  
  
  CONCLUSIONS
  The findings suggest that inhibited production of proinflammatory cytokines may be an extrarenal mechanism that contributes to the beneficial effect of SPIR in patients with CHF.
authors.affiliation: Department of Cardiology P, Gentofte University Hospital, DK-2900 Hellerup, Denmark.
authors.forename: Peter Riis
authors.initials: PR
authors.lastname: Hansen
authors.forename: Klaus
authors.initials: K
authors.lastname: Rieneck
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D002191:Canrenoic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D017373:Cyproterone Acetate / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011245:Pregnadienes / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D011245:Pregnadienes; D012333:RNA, Messenger; D013148:Spironolactone; D000450:Aldosterone; D017373:Cyproterone Acetate; D002191:Canrenoic Acid