title: Transforming growth factor-beta1 blocks in vitro cardiac myocyte depression induced by tumor necrosis factor-alpha, interleukin-1beta, and human septic shock serum.
abstract: OBJECTIVE
  Serum from patients with septic shock induces depression of myocyte contractility in vitro that is proportional the reduction of ejection fraction in vivo. This effect is mediated, in part, by tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Transforming growth factor (TGF)-beta is an immunomodulatory cytokine with a broad range of anti-inflammatory effects. Using an in vitro assay, this study sought to determine the effect of TGF-beta1 on myocyte depression induced by TNF-alpha, IL-1beta, and serum with known depressant activity from patients with septic shock.
  
  
  METHODS
  The maximum extent of shortening of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed-loop video tracking system. Myocytes were exposed to different combinations of TNF-alpha, IL-1beta, septic serum, and TGF-beta1.
  
  
  METHODS
  Basic research laboratory.
  
  
  RESULTS
  Increasing concentrations of TNF-alpha and IL-1beta each caused significant depression of maximum extent of myocyte shortening in vitro over 30 mins (p<.0001). Similarly, a synergistic combination of TNF-alpha and IL-1beta as well as serum with known depressant activity from five patients with acute septic shock induced significant depression of cardiac myocyte contraction (p<.01). Increasing concentrations of TGF-beta1 alone had no effect on maximum extent of cardiac myocyte contraction. However, myocytes that were co-incubated with increasing concentrations of TGF-beta1 demonstrated dose-dependent reversal of depression induced by TNF-alpha or IL-1beta (p<.0001). Similarly, depressant effects caused by synergistic concentrations of TNF-alpha and IL-1beta and serum from all five patients with septic shock were prevented by co-incubation with TGF-beta1.
  
  
  CONCLUSIONS
  These data demonstrate that depression of in vitro cardiac myocyte contraction induced by proinflammatory cytokines and septic serum can be blocked by TGF-beta1. TGF-beta1 may have potential as therapy for sepsis-associated myocardial depression in humans.
authors.affiliation: Section of Critical Care Medicine, Division of Cardiovascular Diseases and Critical Care Medicine, Cooper Hospital/University Medical Center, Robert Wood Johnson Medical School, UMDNJ, Camden, NJ, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
authors.forename: Aseem
authors.initials: A
authors.lastname: Kumar
authors.forename: Bhanu
authors.initials: B
authors.lastname: Paladugu
authors.forename: Joel
authors.initials: J
authors.lastname: Mensing
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parrillo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D044967:Serum / Q000502:physiology*; D012772:Shock, Septic / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha