Role of lipid A of endotoxin in the production of tumour necrosis factor.

Bacterial lipopolysaccharide (LPS) induces the release of tumour necrosis factor (TNF) into serum of mice previously infected with Listeria monocytogenes or immunized with formalin-killed Corynebacterium parvum. This release is greatly reduced by neutralisation of lipid A of LPS with the antibiotic polymyxin B sulfate. The effect is dose-dependent. Base-hydrolysed LPS, which is devoid of lipid A, cannot induce TNF release. Crude lipid A still retains its ability to induce TNF release but is significantly less effective than native LPS molecules. LPS neutralised by polymyxin B also loses its ability to cause high mortality in C. parvum primed mice. These results suggest that lipid A of LPS molecule is important in causing lethality and TNF release in vivo while the polysaccharide portion may be involved in delivering the lipid A moiety to TNF-producing cells.