No abstract

ABSTRACT‐ Bacterial endotoxins are known to be an important cause of cholestasis, yet not all organisms that cause cholestasis produce endotoxins. In order to determine whether bacterial products other than endotoxins may be involved in the cholestatis process, 14C‐taurocholate (TC) uptake by isolated rat hepatocytes was measured in the presence of mid‐log, stationary and mid‐death phase bacterial broth supernatants from eight common bacterial pathogens. The results were then correlated with a quantitative assessment of endotoxin production by each organism. Supernatants from Haemophilus influenzae, Pseudomonas aeruginosa and Klebsiella pneumonia demonstrated a striking inhibitory effect on bile salt uptake (77.2 ± 6.7, 46.9 ± 6.5 and 32.9 ± 7.1% maximum inhibition of 14C‐TC uptake, respectively) when compared to sterile broth controls. Streptococcus faecalis (Enterococcus), Escherichia coli, Staphylococcus aureus and Bacteroides fragilis products, on the other hand, had relatively minor effects (12.3 ± 5.2, 12.0 ± 7.5, 8.4 ± 6.7 and < 5.0% inhibition respectively), while those from Proteus mirabilis had an intermediate effect (18.5 ± 8.3% inhibition). Bile salt efflux rates (16.0 ± 2.7 and 25.1 ± 4.2 nmol/min/106 hepatocytes, mean ± SEM) were similar in bacteria demonstrating marked uptake inhibition (Haemophilus influenzae, Pseudomonas aeruginosa) when compared to those with only minor inhibitory effects (Staphylococcus aureus, Bacteroides fragilis) (14.3 ± 1.1 and 18.4 ± 2.6 nmol/min/106 hepatocytes, respectively, p > 0.05). 14C‐TC uptake inhibition did not correlate with the amount of endotoxin produced by each organism (r = 0.251). The results of this study indicate that bacteria produce a factor other than endotoxin that significantly inhibits bile salt uptake by isolated rat hepatocytes. It is conceivable that this factor not only contributes to the cholestasis caused by endotoxin‐producing organisms but could also play an important role in the cholestasis caused by infection with non‐endotoxin producing bacteria.