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] |