All lipoproteins are able to bind to bacterial lipopolysaccharide (LPS), thereby neutralizing its deleterious effects. However, we demonstrated, recently, that in the absence of apolipoprotein E (apoE), eight‐fold increased very‐low‐density lipoprotein levels were not sufficient to protect apoE‐deficient (apoE^−/−) mice against LPS. During a live Gram‐negative infection, mechanisms other than LPS‐neutralization may play a role in the pathogenesis of the disease. In the present study we further examined the role of apoE in Gram‐negative sepsis.

Survival, bacterial outgrowth in liver, spleen, kidneys and blood, and tumour necrosis factor‐α (TNF‐α) production were measured in apoE^−/− mice and control C57BL/6J mice, after an intravenous infection with Klebsiella pneumoniae.

Mice that lack apoE showed higher mortality in response to K. pneumoniae than control mice (90% vs. 23% respectively after 2 weeks). ApoE^−/− mice had 10–100 times more outgrowth of the bacteria in their organs than controls. Furthermore, circulating TNF‐α concentrations 90 min after a challenge, were almost twice as high in the apoE^−/− mice compared to controls (13.0 ± 2.9 ng mL⁻¹ vs. 7.6 ± 3.8 ng mL⁻¹). When apoE^−/− and control mice were rendered neutropenic, the discrepancy in survival and outgrowth of K. pneumoniae disappeared.

The apoE^−/− mice were more susceptible than control C57BL/6 mice to a K. pneumoniae infection. The absence of apoE may render these mice more susceptible, since this protein is of importance in the detoxification of lipopolysaccharide of Gram‐negative bacteria. On the other hand, the phagocytic capacity of granulocytes seems to be decreased in apoE^−/− mice, resulting in increased outgrowth and mortality.