BACKGROUND: Hematopoietic stem cell transplantation (SCT) carries a significant risk of severe therapy-associated complications chief among which is acute graft vs.host disease (aGVHD). Animal models indicate that myeloablative chemotherapy compromises the mucosal barrier, thereby allowing translocation of intestinal flora-derived lipopolysaccharides (or endotoxin) that subsequently trigger aGVHD, but there are no comparable data in humans. Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT. METHODS: Plasma concentrations of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured in 57 pediatric patients undergoing SCT. In addition plasma endotoxin levels were measured in 25 patients. RESULTS: The previously described rise in CRP was confirmed, and a marked elevation of LBP was observed that peaked at Day 7 (median value, 6.6 microg/ml; P < 0.03 for all pairwise comparisons). CRP and LBP values were significantly correlated (r = 0.77, P < 0.001). A significant but complex relationship was noted between LBP concentrations at Day 0 and severity of subsequent aGVHD (P = 0.02). Of the 25 patients assayed, 11 (44%) had detectable endotoxemia, including 4 who were endotoxin-positive at Day 0. CONCLUSIONS: The detection of endotoxemia coupled with marked elevations in LBP at Day 7 raises the possibility that inflammatory responses early after SCT may be driven in part by the entry of lipopolysaccharide into the bloodstream.
BACKGROUND: Hematopoietic stem cell transplantation (SCT) carries a significant risk of severe therapy-associated complications chief among which is acute graft vs.host disease (aGVHD). Animal models indicate that myeloablative chemotherapy compromises the mucosal barrier, thereby allowing translocation of intestinal flora-derived lipopolysaccharides (or endotoxin) that subsequently trigger aGVHD, but there are no comparable data in humans. Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT. METHODS: Plasma concentrations of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured in 57 pediatric patients undergoing SCT. In addition plasma endotoxin levels were measured in 25 patients. RESULTS: The previously described rise in CRP was confirmed, and a marked elevation of LBP was observed that peaked at Day 7 (median value, 6.6 microg/ml; P < 0.03 for all pairwise comparisons). CRP and LBP values were significantly correlated (r = 0.77, P < 0.001). A significant but complex relationship was noted between LBP concentrations at Day 0 and severity of subsequent aGVHD (P = 0.02). Of the 25 patients assayed, 11 (44%) had detectable endotoxemia, including 4 who were endotoxin-positive at Day 0. CONCLUSIONS: The detection of endotoxemia coupled with marked elevations in LBP at Day 7 raises the possibility that inflammatory responses early after SCT may be driven in part by the entry of lipopolysaccharide into the bloodstream.
Authors: Christine D Palmer; Christy J Mancuso; Jerrold P Weiss; Charles N Serhan; Eva C Guinan; Ofer Levy Journal: J Leukoc Biol Date: 2011-06-07 Impact factor: 4.962
Authors: Eva C Guinan; Christine D Palmer; Christy J Mancuso; Lisa Brennan; Liat Stoler-Barak; Leslie A Kalish; Eugenie E Suter; Leighanne C Gallington; David P Huhtelin; Maria Mansilla; Ralf R Schumann; Jeffrey C Murray; Jerrold Weiss; Ofer Levy Journal: Innate Immun Date: 2013-10-09 Impact factor: 2.680
Authors: Rachel E Crossland; Jean Norden; Mateja Kralj Juric; Kim F Pearce; Clare Lendrem; Louis A Bibby; Matthew Collin; Hildegard T Greinix; Anne M Dickinson Journal: Front Immunol Date: 2017-11-10 Impact factor: 7.561
Authors: Eva Guinan; David E Avigan; Robert J Soiffer; Nancy J Bunin; Lisa L Brennan; Ilana Bergelson; Spencer Brightman; Al Ozonoff; Patrick J Scannon; Ofer Levy Journal: F1000Res Date: 2015-12-21