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Dissociation of IFN- from IL-12 and IL-18 production during endotoxin tolerance

Unité d'Immuno-Allergie, Institut Pasteur, Paris, France

Catherine Fitting

Unité d'Immuno-Allergie, Institut Pasteur, Paris, France

Jean-Marc Cavaillon

Unité d'Immuno-Allergie, Institut Pasteur, Paris, France, jmcavail{at}pasteur.fr

Endotoxin tolerance was induced in mice following one, two or three injections of low amounts of lipopolysaccharide (LPS) before a further LPS injection, and circulating cytokines were analyzed 1.5 h and 3 h after LPS challenge. Three different patterns of cytokine production were obtained. In a first group of cytokines, including tumor necrosis factor (TNF), interleukin-6 (IL-6) and gamma interferon (IFN-), the reduction of plasma peak levels was already significantly pronounced after one tolerizing injection of LPS. The second group of cytokines includes the CC chemokine KC, the CXC chemokine monocyte-chemo-attractant protein-1 (MCP-1) and IL-12. The plasma levels of these cytokines were modestly reduced, and the reduction was more pronounced with increasing numbers of tolerizing injections of LPS. The third group of cytokines includes IL-1ß and IL-18, the levels of which 3 h after LPS challenge (i.e. at the peak timing) remained essentially similar to those of control mice and after 1.5 h were even enhanced. Altogether, these data illustrate that, in tolerized animals, in vivo regulation of cytokine production differs greatly among different mediators and that immunoparalysis is not a general state. Furthermore, despite the presence of large amounts of IL-12 and IL-18, IFN- was essentially suppressed in tolerized animals.

Journal of Endotoxin Research, Vol. 5, No. 5-6, 319-324 (1999)
DOI: 10.1177/09680519990050050801


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