Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs

Wagner, Kristin; Martı́nez, José M.; Vath, Steven D.; Snider, Richard H.; Nylen, Eric; Becker, Kenneth L.; Müller, Beat; White, Jon

doi:10.1097/00003246-200210000-00021

Cited by 100 publications

(68 citation statements)

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“…| IL-1b serum concentration over a 72-hour-period of one horse with an acute colic (Nylen et al 1998, Wagner et al 2002, Martinez et al 2001 (Gogos et al 2000). Beim Menschen bilden IL-1b, IL-6 und TNFa auch den Stimulus für eine Hyperprocalcitoninämie (Redl et al 2000, Redl et al 2001, Whang et al 2000.…”

Section: Abb3unclassified

“…PCT bietet eine kurze Induktionszeit nach bakteriellem Stimulus und eine lange Halbwertszeit (Prkno et al 2013). Auch bei Hamstern, Schweinen, Ratten und Affen wurde ein PCT-Anstieg nach experimentell induzierter Endotoxämie beobachtet, was PCT zu einem möglichen Biomarker für bakterielle Entzündungen in der Veterinärmedizin macht (Zannoni et al 2012, Redl et al 2001, Wagner et al 2002. Beim Pferd konnten in Untersuchungen bei septischen (Rieger et al 2014) …”

Section: Introductionunclassified

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Procalcitonin in horses with an acute colic

Teschner¹,

Rieger²,

Koopmann³

et al. 2015

PHK

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Zusammenfassung: Procalcitonin (PCT) wird in der Humanmedizin als sensitiver Marker für das Vorliegen einer Endotoxämie und bakteriellen Infektion genutzt. In dieser Studie wurde PCT bei endotoxämischen Pferden, bedingt durch eine akute Kolik, bestimmt und mit den proinflammatorischen Zytokinen IL-1b, IL-6 und TNFa verglichen. Ziel dieser Untersuchung war zu beleuchten, ob sich die PCT-Plasmakonzentration bei einer akuten Kolik im Vergleich zum gesunden Pferd erhöht, im Verlauf einer Kolik verändert und ob sie sinnvoll zur Prognosestellung herangezogen werden kann. Schlüsselwörter: Pferd / Kolik / Endotoxämie / Procalcitonin / Zytokine Procalcitonin in horses with an acute colicIn comparison to other animal species the horse is very sensitive to the systemic consequences of endotoxemia leading to a high morbidity and mortality of gastrointestinal (e.g. colic or colitis) disease. Procalcitonin (PCT) is used in human medicine as a sensitive marker for the presence of a bacterial infection and endotoxemia. In this study, PCT was determined in endotoxemic horses with an acute colic and compared to the proinflammatory cytokines IL-1b, IL-6 and TNFa. The aim of this study was to examine whether the PCT plasma concentrations increases in horses with an acute colic compared to healthy horses, changes during the next days after referral to the hospital and whether it can be used to predict survival. 13 horses with an acute colic were classified as endotoxemic based on the results of the clinical and laboratory examination upon admission to the hospital, using a modified score and compared with 20 healthy control horses. For the determination of PCT, IL-1b, IL-6 and TNFa blood was collected from all horses at the time of admission at the equine hospital. Blood samples were quantified at the Helmholtz Zentrum München using an ELISA. A strangulating ileus was diagnosed in 11 horses, an obstructing ileus and enteritis in each case a horse. Endotoxemic horses with an intestinal strangulation showed significantly higher concentrations of median PCT and IL-1b in plasma or serum than the healthy control group. Horses that underwent laparotomy also had significantly higher PCT and IL1-b-plasma or serum concentrations than healthy controls. A follow up measurement of IL-1b and PCT over a 72-hour-period at 7 horses showed no significant changes in the levels. Significantly low median IL-6 serum levels could be measured in the patients when compared to healthy horses. The median serum concentrations of TNFa showed no significant differences between endotoxaemic and healthy horses. A correlation between PCT and IL-1b and survival of patients could not be established. PCT seems to be a promising biomarker for the detection of endotoxemia for the equine medicine but further research is needed.

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Section: Introductionunclassified

Procalcitonin in horses with an acute colic

Teschner¹,

Rieger²,

Koopmann³

et al. 2015

PHK

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“…This was shown in several mammal species, e.g. hamsters [1], pigs [20,21], monkeys [22] and humans [5,23]. Thus, under septic circumstances, the entire body could be viewed as being an endocrine gland.…”

Section: Calcitonin Peptides Are Prototypes Of Hormokinesmentioning

confidence: 99%

Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators

Christ‐Crain¹,

Müller²

2007

European Respiratory Journal

221

149

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Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term ''hormokine'' encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.

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“…Its precise role during sepsis is not fully understood, but it has been shown, in animal models of sepsis, that procalcitonin administration increased mortality and that antibody neutralization of procalcitonin improved survival. [5][6][7] Numerous studies have evaluated the accuracy of determination of procalcitonin compared to C-reactive protein for the diagnosis of bacterial infection. In a metaanalysis that included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients, procalcitonin level was more sensitive (88% [95% CI 80 -93%] vs 75% [95% CI 62-84%]) and more specific (81% [95% CI 67-90%] vs 67% [95% CI 56 -77%]) than C-reactive protein level for differentiating bacterial from noninfectious causes of inflammation.…”

Section: See the Original Study On Page 412mentioning

confidence: 99%