Cytokines and acute heart failure.

Methodist DeBakey Heart Center, The Methodist Hospital, Houston, TX, USA.
Critical care medicine (Impact Factor: 6.37). 02/2008; 36(1 Suppl):S9-16. DOI: 10.1097/01.CCM.0000297160.48694.90
Source: PubMed

ABSTRACT In patients with chronic heart failure, ongoing myocardial injury partially results from activation of the inflammatory system, with production and release of proinflammatory cytokines, activation of the complement system, production of autoantibodies, overexpression of major histocompatibility complex molecules, and expression of adhesion molecules that may perpetuate the inflammatory state. Acute decompensated heart failure modifies the course of chronic heart failure and worsens outcomes via a combination of potential mechanisms, including neurohormonal activation, apoptosis, and the inflammatory cascade. Proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6, play a pathogenetic role in chronic heart failure, and anti-inflammatory immune therapy is currently under investigation. In acute decompensation of chronic heart failure, the change in the inflammatory cytokine activation cascade is less clear. Larger investigational studies are needed to assess the exact roles of circulating and intracardiac cytokines in this particular patient population.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Use of doxorubicin (DOX) is limited by its toxicity in multiple organs. However, the relationship between different organs in response to DOX-induced injury is not well understood. We found that partial hepatectomy correlated with increased DOX-induced heart injury in vivo while supernatant prepared from DOX-treated hepatocytes mitigated DOX-induced cytotoxicity of cardiomyocytes in vitro. Meanwhile, the supernatant of DOX-treated cardiomyocytes mitigated DOX-induced cytotoxicity of hepatocytes. Investigation of the molecular mechanisms underlying these effects found that interleukin 6 (IL-6) was significantly up-regulated in DOX-treated tissues and cells, and supernatant from IL-6 treated cells had a similar effect to that from DOX-treated cells. Although the concentration of secreted IL-6 in supernatant from DOX-treated cells did not significantly differ, blockade of IL-6 signaling, by overexpressing SOCS3, suppressed expression of the downstream molecules trefoil factor family 3 (TFF3) and hepatocyte growth factor (HGF), impaired the mutually beneficial relationship between hepatocytes and cardiomyocytes. In conclusion, our study shows that a mutually beneficial relationship exists between hepatocytes and cardiomyocytes during the acute injury induced by DOX. Moreover, it demonstrates that this phenomenon may be indirectly caused by increased IL-6 expression and the activation of the downstream molecular mediators TFF3 and HGF in hepatocytes and cardiomyocytes, respectively.
    Toxicology Letters 04/2014; · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute heart failure (AHF) is one of the most common causes of hospital admission. Despite the very high short-term morbidity and mortality and high costs associated with the condition, little progress has been made toward an understanding of the complex mechanisms of AHF, and particularly the spike in mortality after AHF admission. This manuscript addresses certain hypotheses for the pathophysiology of increased mortality after an AHF episode, specifically exploring the role of neurohormonal and inflammatory activation, congestion, and end-organ damage occurring during the first hours and days of an AHF episode. The results of the recently published RELAX-AHF (Relaxin in Acute Heart Failure) study may hold the key to understanding these intricate mechanisms. In the study, congestion and end-organ damage, which were strongly associated with increased 180-day mortality, were relieved by early administration of serelaxin, which was also associated with reduction in 180-day mortality. Hence, it is possible that early treatment of AHF, including decongestion and prevention of damage to end organs, including kidneys, heart, and liver, is critical to preventing mortality in AHF. This may require a change in our strategic approach to the management of patients admitted with AHF, setting them apart from patients with chronic heart failure (HF), and developing specific treatment strategies for AHF patients beyond simply implementing therapies proven to be effective in chronic HF.
    Current Heart Failure Reports 12/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: No data from controlled trials exists regarding the inflammatory response in patients with de novo heart failure (HF) complicating ST-elevation myocardial infarction (STEMI) and a possible role in the recovery of contractile function. We therefore explored the time course and possible associations between levels of inflammatory markers and recovery of impaired left ventricular function as well as levosimendan treatment in STEMI patients in a substudy of the LEvosimendan in Acute heart Failure following myocardial infarction (LEAF) trial.
    PLoS ONE 01/2014; 9(11):e112359. · 3.53 Impact Factor