Heat-killed Corynebacterium parvum enhances endotoxin lung injury with increased TNF production in guinea pigs.
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.
Tasaka
S
S
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ishizaka
A
A
Sayama
K
K
Sakamaki
F
F
Nakamura
H
H
Terashima
T
T
Waki
Y
Y
Soejima
K
K
Nakamura
M
M
Matsubara
H
H
Fujishima
S
S
Kanazawa
M
M
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*
D000418:Albumins; D004731:Endotoxins; D008070:Lipopolysaccharides; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha