Preventing the immune system from going haywire during sepsis

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 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 have been developed but little progress has been made.

A group of researchers from Santa Catarina, Rio Grande do Sul and São 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 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.

In a paper entitled "Gastrin-releasing peptide receptor antagonism induces protection from lethal sepsis: involvement of toll-like receptor 4 signaling" and published in Molecular Medicine, the group shows that RC-3095 reduces the levels of circulating TLR-4 and other immune elements associated with an extreme inflammatory response. Additionally, the group has found that patients with septic shock have greater amounts of GRP if compared to those with less severe forms of sepsis. These higher levels of GRP may explain why patients develop multiple organ dysfunctions and present the highest mortality rate among sepsis patients.

The study also shows that in animal models, administration of RC-3095 limits the spread of infection beyond the abdominal cavity, indicating the potential of RC-3095 in preventing the complete breakdown of the host's system.

Besides its clinical relevance, the study provides new insights on the roles of key players involved in the complex communication network triggering extreme inflammatory responses. Together, these findings may open new avenues for the development of effective therapeutic strategies to treat sepsis and related inflammatory diseases.

Provided by Publicase Comunicação Científica

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Doctors to treat septic patients with hypothermia

Jun 30, 2010

Inducing mild hypothermia is easy to implement in clinical practice and may be a valuable tool in the treatment of human sepsis patients, say researchers at the University of Brest, France.

Western diet exacerbates sepsis

Oct 19, 2010

High fat diets cause a dramatic immune system overreaction to sepsis, a condition of systemic bacterial infection. An experimental study in mice, published in the open access journal BMC Physiology, has shown that a diet ...

Surviving sepsis program -- increased compliance gets results

Sep 03, 2009

A 'surviving sepsis' in-hospital project has been shown to improve the care of patients with sepsis. The educational program for early management of patients with septic shock, described in BioMed Central's open access journal ...

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments