HEAT-KILLED CORYNEBACTERIUM-PARVUM ENHANCES ENDOTOXIN LUNG INJURY WITH INCREASED TNF PRODUCTION IN GUINEA

Corynebacterium parvum (CP) is known to increase susceptibility to end otoxin, which is associated with increased production of tu mor necros is factor (TNF). We investigated the effect of CP-priming on the patho genesis of acute lung injury caused by intratracheal Escherichia coli endotoxin (lipopolysaccharide [LPS]). Guinea pigs were divided into fo ur 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 int raperitoneally 7 d before the study. Animals were observed for 4 h aft er intratracheal administration of 0.02 mg/kg of LPS. The lung wet-to- dry weight ratio (W/D), [I-125]albumin concentration ratio of lung tis sue to plasma (T/P) and of bronchoalveolar ravage (BAL) fluid to plasm a (B/P) and differential cell count in BAL fluid were examined. In the LPS-alone group, neither excess lung water nor increased albumin leak age was observed. The CP + LPS group showed increased lung water and a lbumin 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 pretreate d 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 acu te lung injury in parallel with increasing TNF production, which sugge sts that the activation of mononuclear phagocytes contributes to incre ased susceptibility to intratracheal endotoxin in guinea pigs.