The Complementary Action of the Alternative Immunologic Pathway to Improve Sepsis Survival.

Background

Sepsis remains one of the leading causes of death around the world. For many years, sepsis was thought to activate the systemic inflammatory response syndrome in the presence of infection. We now know that this is not true. The current definition of sepsis is a dysregulated host response to infection resulting in organ failure. We sought to examine the literature for evidence of the lectin and alternative pathways (APs) to determine if there is evidence of further dysregulation of these pathways or if they may play a role in compensation for classical pathway dysregulation.

Methods

PubMed was searched for evidence about elements of the classical pathway and APs, and their relationship to survivability in sepsis. Key terms are the classical pathway, the AP, the lectin pathway, sepsis, immunologic dysregulation in sepsis, and metabolic dysregulation in sepsis.

Results

Patients with dysregulated activation of the classical pathway (toll-like receptor 4) cannot contain the pathogen and will develop sepsis. In septic patients, those who can elicit the response of the AP are better able to overcome sepsis than those who cannot. Limited evidence suggests that chronic activation of the AP in asthma protects against sepsis mortality.

Conclusions

This analysis provided insight into innate immune dysregulation in sepsis, offering evidence to serve as a detailed model of the directionality of immunologic dysregulation in sepsis. Evidence of the alternative immune pathways' capacity to complement the immune response shows a relationship to decreased mortality in sepsis. Future research needs to be done to map out the failure of the innate response and develop targeted immune therapies.