Procalcitonin and proinflammatory cytokine interactions in sepsis

Document Type

Journal Article

Publication Date

1-1-1999

Journal

Shock

Volume

12

Issue

4

DOI

10.1097/00024382-199910000-00004

Abstract

Immunoneutralization of procalcitonin (ProCT), a putative mediator of sepsis, has been shown to increase survival in an animal model of sepsis. To better understand the role that ProCT plays in the sepsis cascade, we studied the relationship of this hormone to the proximal proinflammatory mediators, IL-1β and TNFα. Hamsters were made septic by i.p. implantation of Escherichia coli-impregnated agar pellets. A time line study of serum IL-β, TNFα, and ProCT levels showed that the increase in the cytokines was transient and less than 2-fold over baseline, whereas ProCT increased >100-fold by 12 h and remains elevated through 24 h. TNFα (400 μg/kg) was injected into healthy animals, inducing an elevation in ProCT that was 25-fold greater than controls. ProCT (30 μg/kg) was given to healthy and septic animals. In healthy animals, there was no significant elevation in serum IL-1β or TNFα levels. In septic animals, IL-1β was modestly blunted at 3 h but not at 12 h, and there was no change in TNFα levels. ProCT did not initiate or enhance IL-1β or TNFα expression; however, the massive and sustained elevation of this hormone seen in sepsis can be induced by the proximal cytokine, TNFα. This study suggests that ProCT is a secondary mediator that might augment and amplify but does not initiate the septic response. Immunoneutralization of ProCT may prove to be an important clinical strategy, in view of its sustained elevation and the difficulty in initiating therapy for sepsis during the early phases of illness.

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