Inflammatory Response to Different Toxins in Experimental Sepsis Models

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated with early sepsis. This model classically uses lipopolysaccharide (LPS) from Gram-negative pathogens to activate the immune system, leading to hyperinflammation, microcirculatory disturbances and death. Other toxins may also be used to activate the immune system including Gram-positive peptidoglycan (PG) and lipoteichoic acid (LTA). In addition to these standard toxins, other bacterial components can induce inflammation. These molecules activate different signaling pathways and produce different physiological responses which can be taken advantage of for sepsis modeling. Endotoxemia modeling can provide information on pathways to inflammation in sepsis and contribute to preclinical drug development.

Keywords: endotoxemia; infection; inflammation; sepsis.

Figure 1

Gram-positive and Gram-negative bacterial pathogen-associated molecular patterns (PAMPs) interact with various membrane-bound and cytosolic receptors within the host cell. LPS—lipopolysaccharide, PG—peptidoglycan, LTA—lipoteichoic acid, TLR—toll-like receptor, NOD—nucleotide-binding oligomerization domain-containing protein, NAIP—NOD-like receptor apoptosis inhibitory protein, HBP—heptose-1,7-bisphosphate, ALPK1—alpha-kinase 1.