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Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Immunology 2015 ; 144 (3): 405-11 Nephropedia Template TP
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Combined treatment with a CXCL12 analogue and antibiotics improves survival and neutrophil recruitment and function in murine sepsis #MMPMID25201453
Guan S; Guo C; Zingarelli B; Wang L; Halushka PV; Cook JA; Fan H
Immunology 2015[Mar]; 144 (3): 405-11 PMID25201453show ga
Previous studies demonstrated that the CXCL12 peptide analogue CTCE-0214 (CTCE) has beneficial effects in experimental sepsis induced by caecal ligation and puncture (CLP). We examined the hypothesis that CTCE recruits neutrophils (polymorphonuclear leucocytes; PMN) to the site of infection, enhances PMN function and improves survival of mice in CLP-induced sepsis with antibiotic treatment. Mice with sepsis (n = 15) were administered imipenem (25 mg/kg) and CTCE (10 mg/kg) subcutaneously versus vehicle control at designated intervals post-CLP. CTCE treatment increased PMN recruitment in CLP-induced sepsis, as evidenced by increased PMN in blood, by 2·4 ± 0·6 fold at 18 hr, 2·9 ± 0·6 fold at 24 hr, and in peritoneal fluid by 2·0 ± 0·2 fold at 24 hr versus vehicle control. CTCE treatment reduced bacterial invasion in blood [colony-forming units (CFU) decreased 77 ± 11%], peritoneal fluid (CFU decreased 78 ± 9%) and lung (CFU decreased 79 ± 8% versus CLP vehicle). The improved PMN recruitment and bacterial clearance correlated with reduced mortality with CTCE treatment (20% versus 67% vehicle controls). In vitro studies support the notion that CTCE augments PMN function by enhancing phagocytic activity (1·25 ± 0·02 fold), increasing intracellular production of reactive oxygen species (32 ± 4%) and improving bacterial killing (CFU decreased 27 ± 3%). These composite findings support the hypothesis that specific CXCL12 analogues with ancillary antibiotic treatment are beneficial in experimental sepsis, in part, by augmenting PMN recruitment and function.