Toll-like receptors and opportunities for new sepsis therapeutics.
Serious infection and the patient's response (sepsis) is a serious health problem that, even today, is associated with a mortality rate of 30 %-50 %. The phases of severe sepsis include an early hyperinflammatory response to pathogens and a late immunosuppressed phase. Toll-like receptors (TLRs) are a family of transmembrane innate immune receptors that play a major role in both phases of sepsis. Here, their physiology and the therapeutic strategies employed to date are reviewed. Currently, there are no approved therapies targeting TLRs, but it is anticipated that in the future, the less-studied TLRs, such as TLR3, TLR7, and TLR9, will evolve therapeutic targets, perhaps predominantly with agonists, versus the usual antagonist strategies. Furthermore, accurately characterizing the stage of sepsis will be essential to directing appropriate therapeutic choices.
Critical Care Research Laboratories, Heart + Lung Institute, St. Paul's Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada, V6Z 1Y6, john.boyd@hli.ubc.ca.
John H
JH
Boyd