Ubiquitous expression of the calcitonin-I gene in multiple tissues in response to sepsis

Calcitonin precursors (CTpr), including procalcitonin, are important marker s and also potentially harmful mediators in response to microbial infection s. The source and function of CTpr production in sepsis, however, remains a n enigma. In the classical view, the transcription of the CT-I gene is rest ricted to neuroendocrine cells, in particular the C cells of the thyroid. T o better understand the pathophysiology of CTpr induction in sepsis, we use d an animal model analog to human sepsis, in which bacterial infection is i nduced in hamsters by implanting Escherichia coli pellets ip. Compared with control hamsters, levels of CTpr mere elevated several fold in septic plas ma and in nearly all septic hamster tissues analyzed. Unexpectedly, CT-mess enger RNA was ubiquitously and uniformly expressed in multiple tissues thro ughout the body in response to sepsis. Notably, the transcriptional express ion of CT-messenger RNA seemed more widely up-regulated in sepsis than were classical cytokines (e.g. tumor necrosis factor-alpha and interleukin-6). Our findings, which describe a potentially new mechanism of host response t o a microbial infection mediated by CTpr, introduce a new pathophysiologica l role for the CT-I gene.