Adaptation to bacterial lipopolysaccharide controls lipopolysaccharide-induced tumor necrosis factor production in rabbit macrophages.

J C Mathison; G D Virca; E Wolfson; P S Tobias; K Glaser; R J Ulevitch

doi:10.1172/JCI114542

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Find articles by Mathison, J. in: PubMed | Google Scholar

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Find articles by Virca, G. in: PubMed | Google Scholar

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Find articles by Wolfson, E. in: PubMed | Google Scholar

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Find articles by Tobias, P. in: PubMed | Google Scholar

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Find articles by Glaser, K. in: PubMed | Google Scholar

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Find articles by Ulevitch, R. in: PubMed | Google Scholar

Published in Volume 85, Issue 4 on April 1, 1990
J Clin Invest. 1990;85(4):1108–1118. https://doi.org/10.1172/JCI114542.
© 1990 The American Society for Clinical Investigation

Published April 1, 1990 - Version history

These experiments provide an explanation for the observation that two intravenous injections of lipopolysaccharide (LPS) spaced 5 h apart in rabbits cause tumor necrosis factor/cachectin (TNF) levels to rise in the blood only after the first LPS injection. Herein we show that treatment of elicited peritoneal exudate rabbit macrophages (PEM) with two doses of LPS given 9 h apart results in a marked reduction in TNF production by the second LPS exposure. This state of hyporesponsiveness is a result of adaptation to LPS, is induced by LPS concentrations that are 1,000-fold less than required to induce TNF production (picograms vs. nanograms), is characterized by a decrease in LPS-induced TNF mRNA without any change in TNF mRNA half-life, is not changed by including indomethacin in cultures, and is specific for LPS since LPS-adapted cells display a TNF response to heat-killed Staphylococcus aureus that is at least as good as that observed in control PEM.

Images.