Novel approaches to the development of anti-sepsis drugs.
BACKGROUND
Sepsis is the dysregulated systemic immune response to an infection. Experimental and clinical research provided detailed insight into the pathophysiology of the disease, but no pathway explored, so far, has been exploited to deliver effective therapies with regard to significant outcome improvement. Increasing incidence and high mortality of sepsis require novel approaches for the development of anti-sepsis drugs.


METHODS
Since accurate assessment of the patient's condition in sepsis is the basis for the success of novel anti-sepsis drugs, the authors first review briefly biomarkers for improved diagnostics in sepsis. The authors then discuss specific pharmacological approaches with a focus on immune modulation, for example, Toll-like receptor 4 inhibition and modulation of the endocannabinoid system. The authors also cover iron chelation and uncoupling of the nitric oxide pathway.


CONCLUSIONS
The failure of anti-sepsis treatments in the past is most likely related to wrong timing of the drugs due to missing reliable biomarkers to assess the condition of the patients. The authors believe that the development of anti-sepsis drugs using time-critical ('vertical') and continuous ('horizontal') approaches may provide the answer for future novel therapeutics.
Dalhousie University, Department of Anaesthesia , 10 West Victoria, 1276 South Park St., Halifax, Nova Scotia, B3H 2Y9 , Canada +1 902 473 2331 ; +1 902 423 9454 ; chlehmann@dal.ca.
Christian
C
Lehmann
Nivin
N
Sharawi
Nadia
N
Al-Banna
Nathan
N
Corbett
Joshua W
JW
Kuethe
Charles C
CC
Caldwell
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects*; D058990:Molecular Targeted Therapy; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015415:Biomarkers