title: Progressive, severe lung injury secondary to the interaction of insults in gastric aspiration.
abstract: This study examines lung injury and inflammation over 24 hours following intratracheal instillation of hydrochloric acid (acid), small nonacidic gastric particles (SNAP), or combined acid and small particles (CASP) in adult rats. The severity and duration of injury was significantly greater for CASP compared to acid or SNAP based on PaO2/FiO2, bronchoalveolar lavage (BAL) albumin, and BAL cell numbers. The inflammatory response associated with aspiration injury from CASP was distinct in several respects. Tumor necrosis factor (TNF)-alpha was greatly reduced in CASP compared to SNAP or acid, whereas interleukin (IL)-1beta was increased. Levels of cytokine-induced neutrophil chemoattractant (CINC)-1, monocyte chemoattractant protein (MCP)-1, and IL-10 in lavage were also significantly increased in animals injured with CASP compared to other forms of aspiration. Statistical analysis showed that BAL levels of IL-10 correlated most strongly with albumin leakage in aspiration-injured animals at 6 and 24 hours, followed by BAL levels of MCP-1. Additional cytokine cluster analyses indicated that levels of MCP-1 and CINC-1 in BAL from all injured animals were strongly correlated with inflammatory neutrophil numbers at 6 and 24 hours post aspiration, and that IL-10 levels in BAL were strongly correlated with inflammatory cell numbers at 24 hours. Preliminary blocking experiments showed that administration of anti-IL-10 antibody increased the albumin permeability index at 6 hours in SNAP and CASP animals, but anti-MCP-1 antibody did not affect the severity of injury. The results of this study support the possibility that different forms of aspiration are associated with identifiable cytokine profiles, and that specific cytokines, including IL-10 and MCP-1, may have utility as diagnostic or prognostic markers in clinical applications.
authors.affiliation: Departments of Anesthesiology and Microbiology, State University of New York (SUNY) at Buffalo, Buffalo, New York 14214, USA. pknight@buffalo.edu
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: Nader D
authors.initials: ND
authors.lastname: Nader
authors.forename: Jadwiga D
authors.initials: JD
authors.lastname: Helinski
authors.forename: Cristi J
authors.initials: CJ
authors.lastname: Marschke
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Russo
authors.forename: Alan D
authors.initials: AD
authors.lastname: Hutson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Notter
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Holm
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005744:Gastric Acid; D005766:Gastrointestinal Contents; D006851:Hydrochloric Acid; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D011015:Pneumonia, Aspiration / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006851:Hydrochloric Acid