CXCR1/2 blockade to enhance response to immune checkpoint inhibition in an aggressive orthotopic pancreatic adenocarcinoma model
JOURNAL OF CLINICAL ONCOLOGY
Authors: Ullman, Nicholas A.; Ruffolo, Luis I.; Jackson, Katherine M.; Chacon, Alexander; Georger, Mary; Jewell, Rachel; Belt, Brian A.; Maeda, Dean; Zebala, John; Linehan, David
Abstract
Individualized significance of the-251 A/T single nucleotide polymorphism of interleukin-8 in severe infections
EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
Authors: Georgitsi, M. D.; Vitoros, V.; Panou, C.; Tsangaris, I.; Aimoniotou, E.; Gatselis, N. K.; Chasou, E.; Kouliatsis, G.; Leventogiannis, K.; Velissaris, D.; Belesiotou, E.; Dioritou-Aggaliadou, O.; Giannitsioti, E.; Netea, M. G.; Giamarellos-Bourboulis, E. J.; Giannikopoulos, G.; Alexiou, Z.; Voloudakis, N.; Koutsoukou, A.
Abstract
Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay. Carriage of the AA genotype was protective from the development of UTI (odds ratio 0.38, p: 0.007) and CAP (odds ratio 0.30, p: 0.004), but not from IAI and BSI. Protection from the development of severe sepsis/septic shock was provided for carriers of the AA genotype among patients with UTI (odds ratio 0.15, p: 0.015). This was accompanied by greater concentrations of circulating IL-8 among patients with the AA genotype. It is concluded that carriage of rs4073 modifies susceptibility for severe infection in an individualized way. This is associated with a modulation of circulating IL-8.
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