Biologicals and lmmunologicals: Septic shock: the continuing challenge for an effective therapy

Abstract

Septic shock resulting from the systemic response to bacterial endotoxin is an increasing prevalent phenomenon that is the thirteenth leading cause of death in the US. An intensive search for effective treatments has, to date, been less than promising. Monoclonal antibodies (Centoxin™, T-88, E5, CDP 571), interleukin-1 antagonists (IL-1ra), tumour necrosis factor - α (TNF-α) antagonists (lisophylline), bactericidal/permeability increasing protein, platelet activating factor antagonists (BB-882, BN-52021, ABT-299), bradykinin antagonists (CP-0127), nitric oxide synthase inhibitors (L-NMA and L-NAA), inhibitors of TNF processing (MDL201112) and LPS binding agents (Nuprex™, NCY - 103) have all been proposed as effective treatments for septic shock. Of these agents, the monoclonal antibodies, IL-1ra and BK antagonists have proven ineffective in extensive clinical trials leading to a significant decrease in market worth and potential viability for the biotechnology companies involved. While it has been suggest...