Am. J. Respir. Crit. Care Med., Vol 153, No. 3, 03 1996, 1047-1055.
Heat-killed Corynebacterium parvum enhances endotoxin lung injury with increased TNF production in guinea pigs
S Tasaka, A Ishizaka, K Sayama, F Sakamaki, H Nakamura, T Terashima, Y Waki, K Soejima, M Nakamura, H Matsubara, S Fujishima and M Kanazawa
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
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.
