Neves-Costa, A. | bioRxiv Science

bioRxiv2019

CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth-differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15 and that Gdf15-deficient animals are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.

immunology↗

bioRxiv2019

Th2 cytokine profile in appendicular lavage fluid is compatible with allergy as an etiology for acute appendicitis

Acute appendicitis is the most frequent surgical abdominal emergency, but its etiology remains poorly understood. Histological examination of the appendix, following its removal due to acute appendicitis, consistently shows features in common with bronchial asthma, suggesting an allergic reaction as a candidate etiologic factor. Here we propose the concept of appendicular lavage and used it to study the levels of the Th2 cytokines IL-4, IL-5 and IL-9 in patients with a clinical diagnosis of acute appendicitis. The study group included 20 patients with a histological diagnosis of phlegmonous appendicitis, 13 patients with gangrenous appendicitis, and a control group of 8 patients with clinical diagnosis of appendicitis but with normal histology. Cytokines levels were higher in acute appendicitis. The difference was more pronounced when comparing phlegmonous appendicitis with non-pathological appendix (p=0.01) for IL-4 (48,3 vs 21,3 pg/mL), IL-5 (29,2 vs 8,0 pg/mL) and IL-9 (34,1 vs 16,6 pg/mL). This Th2 cytokine profile is compatible with the hypothesis of allergy as an etiologic factor for acute appendicitis and may have important implications for the diagnosis, prevention and treatment of this condition.

pathology↗