Sepsis is a major cause of high mortality rate in intensive care units in the USA (71) . Severe sepsis usually leads to organ failure. Currently, over 30 pharmaceutical products have been in the development stage to treat this condition, yet only few have reached the market (72) . Many of these target specific inflammatory mediators have been unsuccessful because of the complex nature of sepsis. For the treatment of sepsis, there are a few products that are being investigated in clinical studies via blocking different mechanisms of the body's innate immune system. Eli Lilly's Xigris ® was one of the few drugs currently available on the market to treat sepsis. Xigris ® is a recombinant human activated protein C that has anti-inflammatory, anti-thrombotic and pro-fibrinolytic properties to block the coagulation cascade which plays a critical role in the development of organ failure due to sepsis (73) . In addition, simvastatin and atorvastatin had also shown to have some non-specific anti-inflammatory effects contributing to their clinical benefits in treating sepsis (63) . However, statins are currently not been considered as a treatment for sepsis. To find a more specific target, scientists have identified TLR4 as one of the candidates in blocking the innate immune system. Only two TLR4 antagonists, E5564 and TAK-242, have made far into the clinical phase (Table III) .