The Pathogenesis of Sepsis and Potential Therapeutic Targets

Abstract

Sepsis is defined as “a life-threatening organ dysfunction caused by a host’s dysfunctional response to infection”. Although the treatment of sepsis has developed rapidly in the past few years, sepsis incidence and mortality in clinical treatment is still climbing. Moreover, because of the diverse manifestations of sepsis, clinicians continue to face severe challenges in the diagnosis, treatment, and management of patients with sepsis. Here, we review the recent development in our understanding regarding the cellular pathogenesis and the target of clinical diagnosis of sepsis, with the goal of enhancing the current understanding of sepsis. The present state of research on targeted therapeutic drugs is also elaborated upon to provide information for the treatment of sepsis.

Can endolysosomal deacidification and inhibition of autophagy prevent severe COVID-19?

“…This pattern of immune and histological abnormalities seen in patients with severe COVID-19 is also seen in sepsis and septic shock [ [36] , [37] , [38] , [39] , [40] ]. Indeed, there is a growing consensus that severe COVID-19 infection may be a distinct form of viral sepsis [ 1 , 41 , 42 ] which has considerable long-term implications for post-discharge as well as in hospital pathology, as discussed below.…”

Platelets as a prognostic marker for sepsis

“…Dysbalanced immune response and activation of the coagulation system during sepsis are fundamental events leading to sepsis complications and organ failure. [ 7 ] The severity of organ dysfunction has a prognostic value, and in clinical practice is usually classified according to the Sequential Organ Failure Assessment (SOFA) score, [ 8 ] platelet is an important role in the SOFA score representing hematological function, hematological failure is common in patients with septic shock. [ 9 ] Platelets catalyze the development of hyperinflammation, disseminated intravascular coagulation and microthrombosis, and subsequently contribute to multiple organ failure.…”

The Effect of Bacterial Endotoxin LPS on Serotonergic Modulation of Glutamatergic Synaptic Transmission

“…Septicemia induced by gram-negative bacteria is life threatening and can trigger a whole-body immune response which can further pathological conditions with elevated levels of released cytokines. Therapeutic treatments of bacterial septicemia vary depending on many conditions of the infection and health status of the person or animal [1]. There is a heavy focus on reducing the effects of the cytokines on target tissue [2,3].…”

“…Along with attempting to target receptors for LPS, there are also many therapeutic approaches to reducing the immune responses [1]. To understand the treatments, one can approach this task from a whole animal or a cellular level using various animal models.…”

“…Therefore, it is of interest to understand how the targets of medications may be influenced by the direct compounding action of LPS. Medications to manage depression and anxiety commonly involve the serotoninergic system on either the reuptake transporters (i.e, SSRIs) or the specific serotonin (5-hydroxytryptamine or 5-HT) receptors [1]. The serotonin receptor subtype 5-HT2A is one of the receptor subtypes targeted due to the relationship with depression and altering mood [6,7].…”