title: Heat-killed Corynebacterium parvum enhances endotoxin lung injury with increased TNF production in guinea pigs.
abstract: Corynebacterium parvum (CP) is known to increase susceptibility to endotoxin, which is associated with increased production of tumor necrosis factor (TNF). We investigated the effect of CP-priming on the pathogenesis of acute lung injury caused by intratracheal Escherichia coli endotoxin (lipopolysaccharide [LPS]). Guinea pigs were divided into four groups: (1) control (n=6), (2) CP-alone (n=6), (3) LPS-alone (n=6) and (4) CP + LPS (n=6). A CP dose of 4 mg/kg was injected intraperitoneally 7 d before the study. Animals were observed for 4 h after intratracheal administration of 0.02 mg/kg of LPS. The lung wet-to-dry weight ratio (W/D), [125I] albumin concentration ratio of lung tissue to plasma (T/P) and of bronchoalveolar lavage (BAL) fluid to plasma (B/P) and differential cell count in BAL fluid were examined. In the LPS-alone group, neither excess lung water nor increased albumin leakage was observed. The CP + LPS group showed increased lung water and albumin leakage as compared with the other three groups (p<0.05). We also observed increased cell counts in BAL fluid (p<0.05), in the CP + LPS group. The spleen weight was increased in guinea pigs pretreated with CP, indicating reticuloendothelial system (RES) activation. In the CP + LPS group, the TNF level was increased in both plasma and BAL fluid. We conclude that pretreatment with CP enhances LPS-induced acute lung injury in parallel with increasing TNF production, which suggests that the activation of mononuclear phagocytes contributes to increased susceptibility to intratracheal endotoxin in guinea pigs.
authors.affiliation: Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tasaka
authors.forename: A
authors.initials: A
authors.lastname: Ishizaka
authors.forename: K
authors.initials: K
authors.lastname: Sayama
authors.forename: F
authors.initials: F
authors.lastname: Sakamaki
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Terashima
authors.forename: Y
authors.initials: Y
authors.lastname: Waki
authors.forename: K
authors.initials: K
authors.lastname: Soejima
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: S
authors.initials: S
authors.lastname: Fujishima
authors.forename: M
authors.initials: M
authors.lastname: Kanazawa
mesh_terms: D000287:Administration, Topical; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004731:Endotoxins / Q000008:administration & dosage / Q000009:adverse effects*; D004926:Escherichia coli; D015633:Extravascular Lung Water / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006358:Hot Temperature; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D012157:Mononuclear Phagocyte System / Q000473:pathology; D009929:Organ Size; D010586:Phagocytes / Q000473:pathology; D011425:Propionibacterium acnes / Q000502:physiology*; D011654:Pulmonary Edema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012709:Serum Albumin / Q000032:analysis; D013154:Spleen / Q000473:pathology; D014132:Trachea; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D000418:Albumins; D004731:Endotoxins; D008070:Lipopolysaccharides; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha