Cardiac inflammation and innate immunity in septic shock: is there a role for toll-like receptors?

Chest. 2002 Apr;121(4):1329-36. doi: 10.1378/chest.121.4.1329.


Our current understanding of the pathogenesis of sepsis suggests that bacteria as well as bacterial-derived products activate an uncontrolled network of host-derived mediators such as proinflammatory cytokines (ie, tumor necrosis factor [TNF] and interleukin [IL]-1beta), which can ultimately lead to cardiovascular collapse and death. Despite the potentially important role that TNF and IL-1beta may play in producing cardiac dysfunction in human septic shock, little is known with regard to the basic biochemical mechanism(s) by which bacterial pathogens induce their expression in the heart. A major advance in understanding the early events that are downstream from bacterial-mediated signaling has been the identification of Toll-like receptors (TLRs). TLR-mediated signaling is known to activate the transcription factor nuclear factor-kappaB and to upregulate TNF expression. It has recently been shown that the heart expresses TLRs, raising the possibility that these receptors may be responsible for mediating the deleterious effects of bacterial pathogens on cardiac function. In this review, we will discuss the emerging role for TLRs in the pathogenesis of the cardiovascular collapse that occurs during sepsis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Drosophila Proteins*
  • Heart Failure / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Interleukin-1 / metabolism
  • Membrane Glycoproteins / physiology*
  • Receptors, Cell Surface / physiology*
  • Systemic Inflammatory Response Syndrome / immunology*
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / physiology


  • Drosophila Proteins
  • Interleukin-1
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha