Human peripheral blood mononuclear cells express mRNA for procalcitonin; modulation by lipopolysaccharides and sepsis related cytokines

Abstract

Background: Whole body hyperthermia induced by radiative systems has been used in therapy of malignant diseases for more than ten years. Von Ardenne and co-workers have developed the 'systemiche Krebs-Mehrschritt-Therapic' (sKMT), a combined regime including whole body hyperthermia of 42°C, induced hyperglycaemia and relative hyperoxaemia with additional application of chemotherapy. This concept has been employed in a phase I/II clinical study for patients with metastatic colorectal carcinoma at the Virchow-Klinikum since January 1997. Methods: The sKMT concept was performed eleven times under intravenous general anaesthesia, avoiding volatile anaesthetics. Core temperatures of up to 42°C were reached stepwise by warming with infrared-A-radiation (IRATHERM 2000®). During the whole procedure blood glucose levels of 380-450 mg/dl were maintained as well as PaO 2 levels above 200 mmHg. Extensive invasive monitoring was performed in all patients including measurements with the REF-Ox-Pulmonary artery catheter with continuous measuring of mixed venous saturation (Baxter Explorer®) and invasive monitoring of arterial blood pressure. Data for calculation of hemodynamic and gas exchange parameters were collected four times, at temperatures of 37°C, 40°C, 41.8-42°C and 39°C, during measurements FiO 2 was 1.0 at all times. Fluids were given in order to keep central-venous and Wedge pressure within normal range during the whole procedure. Statistics were performed using the Wilcoxon Test. Results: Statistically significant differences were found between heart rate, cardiac index and systemic vascular resistance comparing data at 37°C and 42°C. Heart rate and cardiac index increased to a maximum at 42°C (P < 0.0001) whereas systemic vascular resistance had its minimum at 42°C (P < 0.0001). Mean arterial pressure dropped with increasing temperature, differences were not significant. Calculation of stroke volume index and ventricular volumes showed only a slight decrease in endsystolic volumes with increasing temperature, the resulting differences in right ventricular ejection fraction were marginally significant (P = 0.038) comparing 42°C to baseline. Right ventricular stroke work index as well as mean pulmonary arterial pressure increased at 42°C (P = 0.0115 and P = 0.0037), pulmonary vascular resistance only dropped little compared to systemic vascular resistance, left ventricular stroke work index even dropped with increasing temperature, though showing no significant difference. Values for mixed venous oxygen saturation did not vary during therapy, pulmonary right-left shunt showed a temperature associated increase (P = 0.0323) to a maximum at 42°C. Conclusion: Under the procedure of sKMT cardiac function in patients, who do not have any pre-existing cardiac impairment, can be maintained almost unchanged, ie with normal right and left ventricular pressure, despite an increase in right ventricular stroke work Acknowledegment: Supported by Deutsche Krebshilfe.

Procalcitonin as a marker of the systemic inflammatory response to infection

“…One study has shown that TNFa infusion into animals induces procalcitonin production although the levels measured were much lower then those encountered during infection [16]. Our in vitro studies also suggest that endotoxin is a more potent stimulator of procalcitonin mRNA than TNFa or other proinflammatory cytokines [17] (Fig. 1).…”

The role of serum procalcitonin in the diagnosis of bacterial meningitis in adults: a systematic review and meta-analysis

“…It has been hypothesized that this increase is due to the overexpression of the CALC-1 gene and increased release of PCT from various tissues in response to bacterial endotoxins and inflammatory cytokines such as TNF-α, IL-6 and IL-1β [8,[11][12]. Unlike CRP, procalcitonin has not been reported to be elevated in viral infections, thus conferring the important ability to distinguish easily between bacterial and viral etiologies [13].…”

Procalcitonin als monozytärer Marker für die Frühdiagnostik bei septischem Abort*

“…Obwohl es erste Hinweise auf die Expression von inflammatorisch induziertem PCT in mononukleären Zellen des peripheren Blutes gibt [18], konnte eine Freisetzung von PCT aus definierten Zellpopulationen noch nicht belegt werden. Durch den Nachweis von PCT in kultivierten humanen Blutmonozyten und im Überstand dieser Zellkuturen wird unsere Vermutung, wonach Mitglieder des Monozyten/Makrophagensystems entscheidende Bildungsorte der inflammatorisch induzierten PCT sind, bestätigt.…”