Pro-resolving lipid mediators in sepsis and critical illness.

PURPOSE OF REVIEW: Sepsis is a life-threatening condition caused by a dysregulated host response to infection that remains a huge clinical challenge. Recent evidence indicates that bioactive lipid mediators derived from polyunsaturated fatty acids termed specialized pro-resolving mediators (SPMs) are promising new candidates for treating critical illness. RECENT FINDINGS: We highlight herein the protective actions of SPMs in experimental sepsis, cardiac dysfunction, and also lung and cerebral injury, and discuss their mechanisms of action. We also emphasize that failed resolution responses and dysregulated SPM pathways may provide an explanation for the ongoing chronic inflammation in many diseases including chronic heart failure. SUMMARY: Importantly, monitoring plasma SPM profiles can predict patient outcomes in sepsis indicating their utility as new early biomarkers that may help stratify patients upon ICU admission.

Airway dendritic cell maturation in children exposed to air pollution.

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 µg/m3, n = 138), middle (25.6 to 26.8 µg/m3, n = 126), and upper (26.8 to 31.0 µg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of "mature" airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.