Septic shock is the most severe outcome associated with pathogen infection in the bloodstream. It is a life-threatening condition invariably leading to multiple organ dysfunctions. Currently, septic shock is one of the most frequent causes of death in intensive care units worldwide.
However, it is already known that sepsis-induced multiple organ dysfunction is not a direct effect of the pathogen invasion itself but rather an overreaction of the host immune system against the infection. Many strategies aiming at holding back the extreme response of the immune system have been developed but little progress has been made.
A group of researchers from Santa Catarina, Rio Grande do Sul and S-o Paulo, in Brazil, have shown that blocking the receptor of bombesin/gastrin-releasing peptide (GRP), a peptide involved with the activation of neutrophil and macrophage immune cells, improves survival in sepsis animal models. Working with RC-3095, an antagonist of the GRP receptor developed by Nobel Laureate Dr Andrew Schally, the group showed that this molecule attenuates the release of the host's exacerbating immune response elements, and reveals a new inflammatory pathway and potential target for new drugs. The study was part of a research effort to investigate additional functions and potential clinical applications for the GRP receptor, initiated by Drs Gilberto Schwartsmann and Rafael Roesler at the Federal University of Rio Grande do Sul.
Led by Drs Felipe Dal-Pizzol and Fabricia Petronilho at the Universidade do Extremo Sul Catarinense, in Brazil, the group has recently teamed up with Drs Andrew Schally and Norman L. Block at the University of Miami Miller School of Medicine to investigate the potential link between GRP and TLR-4, a receptor found in neutrophils and macrophages. TLR-4 is one of the molecules responsible for spreading the word that the body has been invaded by microbes and that something must be done quickly.