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Ubiquitous Expression of the Calcitonin-I Gene in Multiple Tissues in Response to Sepsis¹

Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School (B.M., J.F.H.), Boston, Massachusetts 02114; and Department of Surgery and Medicine, George Washington University and the Veterans Affairs Medical Center (J.C.W., E.S.N., R.S.S., K.L.B.), Washington, DC 20422

Address all correspondence and requests for reprints to: Beat Müller, Division of Endocrinology, Diabetology and Clinical Nutrition, Department of Internal Medicine, University Hospitals, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: happymiller{at}bigfoot.com

Calcitonin precursors (CTpr), including procalcitonin, are important markers and also potentially harmful mediators in response to microbial infections. The source and function of CTpr production in sepsis, however, remains an enigma. In the classical view, the transcription of the CT-I gene is restricted to neuroendocrine cells, in particular the C cells of the thyroid. To better understand the pathophysiology of CTpr induction in sepsis, we used an animal model analog to human sepsis, in which bacterial infection is induced in hamsters by implanting Escherichia coli pellets ip. Compared with control hamsters, levels of CTpr were elevated several fold in septic plasma and in nearly all septic hamster tissues analyzed. Unexpectedly, CT-messenger RNA was ubiquitously and uniformly expressed in multiple tissues throughout the body in response to sepsis. Notably, the transcriptional expression of CT-messenger RNA seemed more widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis factor- and interleukin-6). Our findings, which describe a potentially new mechanism of host response to a microbial infection mediated by CTpr, introduce a new pathophysiological role for the CT-I gene.

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