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Table 1 Examples of negative human therapeutic trials targeting successive inflammatory pathways involved in the pathophysiology of sepsis

From: Insights and limits of translational research in critical care medicine

Steps of the inflammatory response Target Treatment Included population References
Bacterial components Bacterial membrane Recombinant bactericidal protein (rBPI21) Meningococcal sepsis (n = 393) Levin et al. Lancet 2000 [76]
LPS Murine anti-endotoxin antibody Severe sepsis (n = 1,090) Angus et al. JAMA 2000 [77]
Receptors TLR-4 Lipid antagonist of MD2-TLR4 Severe sepsis (n = 1,961) Opal et al. JAMA 2013 [78]
Intracellular signaling Inflammatory pathways Methylprednisolone (high doses) Severe sepsis (n = 382) Bone et al. N Engl J Med 1987 [79]
Cytokine production TNF-α Soluble TNF receptor Septic shock (n = 141) Fisher et al. N Engl J Med 1996 [18]
IL-1 IL-1 receptor antagonist Severe sepsis (n = 696) Opal et al. Crit Care Med 1997 [80]
Enzyme activation Phospholipase PAF inhibitor BB-882 Severe sepsis (n = 152) Vincent et al. Crit Care Med 2000 [81]
Oxidative stress Reactive oxygen species Selenium Severe sepsis (n = 150) Valenta et al. Intensive Care Med 2011 [82]
  1. LPS, lipopolysaccharide; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor alpha; IL, interleukin; PAF, platelet activating factor.