The outcome of
sepsis and
septic shock has not significantly improved in recent decades despite the development of numerous drugs and supportive care
therapies. To reduce
sepsis-related mortality, a better understanding of molecular mechanism(s) associated with the development of
sepsis and
sepsis-related organ injury is essential. There is increasing evidence that
Toll-like receptors (TLRs) play a key role in the mediation of systemic responses to invading pathogens during
sepsis. However, the role of TLRs in the development of
sepsis and in
sepsis-related organ injury remains debatable. In this review, we focus on the biological significance of TLRs during
sepsis. Medline was searched for pertinent publications relating to TLRs, with emphasis on their clinical and pathophysiological importance in
sepsis. In addition, a summary of the authors' own experimental data from this field was set in the context of current knowledge regarding TLRs. In both animal models and human
sepsis, TLRs are highly expressed on monocytes/macrophages, and this TLR expression may not simply be a
ligand-specific response in such an environment. The fact that TLR signaling enables TLRs to recognize harmful mediators induced by invading pathogens may be associated with a positive feedback loop for the inflammatory response among different cell populations. This mechanism(s) may contribute to the organ dysfunction and mortality that occurs in
sepsis. A better understanding of TLR biology may unveil novel therapeutic approaches for
sepsis.