What is Sepsis?

What is Sepsis?

Sepsis Infection and Inflammation

The immune cells are in charge of produce a response against every pathogen that want to attack ours bodies. This response finish when the pathogen is dead and our system is save again. Nevertheless, in some cases the infection could be important and can be maintained over time, forcing our immune system to generate systemic and aggressive inflammatory mechanisms against them that also can affect our organism. This life-threatening condition is know as sepsis.

Sepsis is leading cause of death in most intensive care units and remains associated with an unacceptable high mortality ranging from 15% to 50% of patients in severe conditions. Reading these numbers, looks imperative generate more effective treatment strategies. Nevertheless, the studies of sepsis turned out to be harder to study because the septic response is heterogeneous and depend on the causative pathogen, microbial load and virulence. This is why sepsis researchers are focused on investigating stages that are common in all types of sepsis and what the role of the cells involved in the inflammatory process is.

Inflammatory Response in Sepsis

At the beginning it was observed that in all cases of sepsis, patients presented a high increase in inflammatory cytokines what was known as ¨Systemic inflammatory response syndrome¨ (SIRS). Based on this information, the researchers attempted to block inflammatory cytokines such as TNF or IL-1 with antibodies, but these studies did not improve the clinical symptoms of this condition. In the late 1990s the scientifics discovered that after cytokine storm phase of sepsis, many septic patients developed an anti-inflammatory state know as ¨compensatory anti-inflammatory response syndrome¨(CARS). After considerable debate, a consensus developed that, sepsis can evolve two phases: hyper-inflammation and hypo-inflammation. In the last time, a debate has persisted as to whether inflammatory or anti-inflammatory processes are more detrimental to sepsis survival. While inflammatory response drive to early mortality in the initial days of sepsis, the compensatory anti-inflammatory response induces mortality several days to weeks later.

Cell-mediated Immunity in Sepsis

Genomic analysis of tissue samples from septic patients suggest that in sepsis induce alterations in all immune cells; in those that produce inflammation as in those that produce anti-inflammation. For this reason, current scientific studies are focused on studying immune cells one by one and their role in sepsis.

The study of the cells of the immune system has allowed to determine modulators, that are molecules that allow to increase or to diminish the function of a particular cellular population, in order to maintain a balance between an inflammatory state and an anti-inflammatory stage. This would increase the survival of patients with sepsis.

Conclusion

A careful balance between the inflammatory and anti-inflammatory response is vital for a successful host response to sepsis. Two decades od failed sepsis trials have forced one to rethink the sepsis paradigm. New human sepsis studies should consider the heterogeneity in the patients, the type of infection and the phenotype predominant in the immune response (pro or anti-inflammatory). Taking this into account, goal-directed immune-modulatory therapy involving multiple agents, may, over time, provide optimal clinical benefit.

8th Jul 2020 Valeria Manriquez, Pasteur Insitute, France

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