Induction of human interleukin 1 by bacterial and synthetic lipid A

Abstract

Lipopolysaccharides (LPS) are well known inducers of interleukin 1 (IL1). Here we show that synthetic heptaacyl Salmonella minnesota (compound 516) and synthetic E. coli type (compound 506) lipid A, as well as monodephospho part structures thereof, are able to induce IL1 production in human mononuclear cells. The 4′-monodephospho part structure (compound 505) was found to be the most active IL1 inducer as compared to compound 506 and the 1-monodephospho part structure (compound 504). Synthetic lipid A precursor Ia, lacking nonhydroxylated fatty acids (compound 406), and its 1- or 4′-monodephospho part structures (compounds 404 and 405) did not induce IL 1 production. IL2 is not produced during stimulation with the synthetic compounds. IL1 activity was partially heat labile and could be inhibited by a rabbit antiserum against human leukocytic pyrogen. These results show that the lipid A component of LPS is active in inducing IL 1 and that the presence of 3-acyloxyacyl residues is necessary for IL1 induction.