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Submitted on July 10, 2003
Accepted on August 12, 2003
1 Department of Research (P.L., D.S.), Division of Endocrinology, Diabetology and Clinical Nutrition (U.K., B.M.), Department of Visceral Surgery (I.L.), and Department of Plastic Surgery (M.S.), University Hospitals, CH-4031 Basel, Switzerland and Dept. of Medicine, George Washington University and Veterans Affairs Medical Center (E.S.N., K.L.B.), Washington, DC 20422
* To whom correspondence should be addressed. E-mail: Philippe.Linscheid{at}unibas.ch.
Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several-thousand-fold in human sepsis and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin-I gene (CALC I) gene expression in human adipocyte primary cultures and in adipose tissue samples from infected and non-infected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, expression of CT-mRNA increased 24-fold (P < 0.05) by the administration of Escherichia coli endotoxin (LPS) and 37-fold (P < 0.05) by interleukin-1
(IL-1
) after 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with LPS treatment and 15.2-fold (P < 0.01) by IL-1
after 48 h. In co-culture experiments, adipocyte CT-mRNA expression was evoked by Escherichia coli activated macrophages, in which CT-mRNA was undetectable. The marked IL-1
-mediated-ProCT release was inhibited by 89% during co-administration with interferon-
(IFN-
). In patients with infection and markedly increased serum ProCT, CT-mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFN-
on IL-1
-induced CT-mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.
interferon-
endotoxin
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