title: Stress induced changes in lymphocyte subpopulations and associated cytokines during whole body hyperthermia of 41.8-42.2 degrees C.
abstract: Extreme acute physical stress leads to transient impairment of T-lymphocytes, which are essential for tumor defence and prevention of infectious diseases. Radiant whole body hyperthermia (WBH) at 41.8-42.2 degrees C may enhance the efficacy of systemic chemotherapy in patients with advanced malignancies, but is associated with marked physical stress. Aim of this study was to demonstrate stress induced short-time effects on lymphocyte subpopulations and associated cytokines during WBH. Total leukocyte count, white blood cell differential blood count, lymphocyte subpopulations (T-helper-/T4-cells, T-suppressor-/T8-cells, natural-killer-/NK-cells, gammadelta-T-cells) as well as plasma levels of Interleukin(IL)-10, IL-12 and Interferon-gamma (IFN-gamma) were measured in ten patients treated with WBH and additional cytostatic chemotherapy. Blood samples were drawn before treatment, at three temperature points during WBH, and 24 h after start of treatment. Results were compared with those obtained from a control group consisting of six patients receiving chemotherapy alone. Numbers of T4-cells decreased significantly during WBH, while numbers of NK-cells and gammadelta-T-cells increased, resulting in transient impairments of total lymphocyte counts and T4/T8-ratio. IL-12 plasma levels as well as IFN-gamma/IL-10-ratio also decreased during WBH. No significant changes were found in T8-cells of WBH patients. Changes were reversible within 24 h and could not been found in control patients. Our results support the hypothesis that WBH combined with chemo therapy induces a strong but reversible anti-inflammatory stress response in cancer patients during therapy. Further studies are necessary to examine the pathophysiological details and to evaluate the meaning of these transient immunological changes for patient's outcome.
authors.affiliation: Klinik für Anästhesiologie und operative Intensivmedizin, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13344, Berlin, Germany. olaf.ahlers@charite.de
authors.forename: Olaf
authors.initials: O
authors.lastname: Ahlers
authors.forename: Bert
authors.initials: B
authors.lastname: Hildebrandt
authors.forename: Annette
authors.initials: A
authors.lastname: Dieing
authors.forename: Maria
authors.initials: M
authors.lastname: Deja
authors.forename: Thomas
authors.initials: T
authors.lastname: Böhnke
authors.forename: Peter
authors.initials: P
authors.lastname: Wust
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.forename: Herwig
authors.initials: H
authors.lastname: Gerlach
authors.forename: Thoralf
authors.initials: T
authors.lastname: Kerner
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010865:Pilot Projects; D013312:Stress, Physiological / Q000276:immunology*
chemical_list: D016207:Cytokines