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Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia

Zirkulierendes Interleukin-6, Interleukin-8, Interleukin-1-beta und Tumor-Nekrose-Faktor-alpha. Kinetik und Korrelation mit der Körpertemperatur bei Patienten mit Neutroponie und Fieber

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Summary

Interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF) are important mediators of fever and inflammation, and are involved in the pathogenesis of sepsis. There is only limited data on serum concentrations of these proinflammatory cytokines in patients with fever and neutropenia, and their interrelationship and correlation with body temperature and clinical disease early in the febrile response during neutropenia have not been studied. Immunoreactive TNF, IL-1β, IL-6, and IL-8 in serum samples serially obtained from 14 adult patients with neutropenia and fever considered or documented to be due to infection were measured. IL-6 and Il-8 were consistently elevated in all patients, and correlated well with each other and with body temperature. Median peak concentration of IL-6 and IL-8 were 400 pg/ml (range: 100 to 41,000 pg/ml), and 1,025 pg/ml (range: 600 to 26,000 pg/ml), respectively, and levels of both cytokines rapidly declined in patients responding to antimicrobial therapy. Despite frequent sampling before and after the temperature peaks TNF and IL-1β, conversely, were less frequently detectable, with median peak values of <10 pg/ml (range: <10 to 150 pg/ml) for TNF, and 17 pg/ml (range: <10 to 36 pg/ml) for IL-1β, respectively. The role of neutro- and monocytopenia with depletion of important cytokine producing and target cells in this particular cytokine response pattern needs to be further studied.

Zusammenfassung

Die Beteiligung der Zytokine Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (II-8) und Tumor-Nekrose-Faktor-alpha (TNF) bei der Sepsis und dem septischen Schock ist gut belegt. Doch existierenden wenige Daten insbesondere zur frühen Kinetik zirkulierender Zytokine bei Patienten mit Fieber und Neutropenie. Daher wurden bei 14 erwachsenen Patienten mit Chemotherapie-induzierter Leukopenie prospektiv bei Auftreten von Fieber Konzentrationbestimmungen dieser Zytokine in konsekutiv entnommenen Serumproben durchgeführt. IL-6 und IL-8 waren bei allen Patienten erhöht und korrelieren gut untereinander und mit dem Fieberverlauf. Der Median der Spitzenwerte lag für IL-6 bei 400 pg/ml (Bereich: 100 bis 41 000 pg/ml), für IL-8 bei 1025 pg/ml (600 bis 26 000 pg/ml). Bei Patienten mit ansprechen auf entsprechende antimikrobielle Therapie kam es zu einem raschen Abfall der Serumkonzentrationen dieser Zytokine. Trotz der engmaschig vor und nach dem Temperaturmaximum entnommenen Proben waren meßbare Konzentrationen von TNF und IL-1b seltener, und die mittleren Spitzenkonzentrationen waren sowohl für TNF mit <10 pg/ml (<10 bis 150 pg/ml) als auch für IL-1β mit 17 pg/ml (<10 bis 36 pg/ml) sehr niedrig. Inwieweit die Neutropenie und Monocytopenie mit der damit verbundenen Depletion wesentlicher Zytokin-produzierender und-Target-Zellen für dieses Zytokin-Sekretionsmuster eine Rolle spielen, sollte weiter untersucht werden.

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  1. Sektion Infektiologie und Klinische Immunologie, Medizinische Universitätsklinik und Poliklinik, D-89070, Ulm, Germany

    A. Engel,  W. V. Kern,  G. Mürdter &  P. Kern

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  1. A. Engel
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  3. G. Mürdter
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Engel, A., Kern, W.V., Mürdter, G. et al. Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia. Infection 22, 160–164 (1994). https://doi.org/10.1007/BF01716695

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