OBJECTIVE: To obtain further insight into the constitutional, phenotype-dependent changes of T-helper-1 and T-helper-2 signature lymphokine synthesis after trauma. DESIGN: Prospective, descriptive study. SETTING: Intensive care unit of a burn center in a community hospital. PATIENTS: Ten patients 1, 3, 5, and 7 days after major burn injury and 15 healthy individuals. INTERVENTIONS: Peripheral blood mononuclear cells were separated and incubated (5 hrs) for cytokine production induced by the accessory cell-independent stimulus of ionomycin and phorbol 12-myristate 13-acetate. After fixation and permeabilization, cell samples were immunofluorescently stained for cell surface antigens (CD4 and CD8), intracellular interferon (IFN)-gamma, and interleukin (IL)-4 synthesis. Results were correlated with corresponding enzyme-linked immunosorbent assay measurements of the culture supernatants. MEASUREMENTS AND MAIN RESULTS: The phenotypic analysis of the composition of the helper (CD4) and suppressor/cytotoxic (CD8) T-cell subset demonstrated that patients suffering from major burns and healthy controls express these antigens in similar percentages. The ratio of CD4 positive to CD8 positive/CD16 negative T-cell subsets showed no significant changes after trauma compared with controls. The production of IL-4 was excessively up-regulated while the release of IFN-gamma was only slightly increased. The predominant cell source of IL-4 after burn trauma was the CD8+ cell with nearly five-fold increased production on day 5 (7.2+/-2.6%) vs. 1.5+/-0.4% in controls. While CD8+ cells are also capable of enhancing their IFN-gamma synthesis under stress by about 60% due to the significant participation of the naive CD45RA+ subset, the CD4+ IFN-gamma release remained largely unchanged. With this study, we demonstrated that in nonsurvivors the number of CD8+ IL-4-producing cells was significantly higher compared with controls; also, the number of IFN-gamma-releasing memory/effector CD45RO+ cells was lower compared with survivors. CONCLUSIONS: In previous experiments, we show that a shift to T(H)2 dominated phenotypes increases the risk for postburn infection. The current study confirms that major burns induce a significant shift of cytokine response in the T(H)2 direction and demonstrates that the CD8+, rather than the CD4+ phenotype, is present. Increased IL-4 production is associated with the T(H)2 lymphocyte. These diagnostic tests may help to differentiate patients with compensatory anti-inflammatory response syndrome and immunosuppression from those patients in the proinflammatory state associated with the systemic inflammatory response syndrome. The profile described in this article is associated with immunosuppression and may contraindicate attempts at anti-inflammatory therapy for sepsis.
OBJECTIVE: To obtain further insight into the constitutional, phenotype-dependent changes of T-helper-1 and T-helper-2 signature lymphokine synthesis after trauma. DESIGN: Prospective, descriptive study. SETTING: Intensive care unit of a burn center in a community hospital. PATIENTS: Ten patients 1, 3, 5, and 7 days after major burn injury and 15 healthy individuals. INTERVENTIONS: Peripheral blood mononuclear cells were separated and incubated (5 hrs) for cytokine production induced by the accessory cell-independent stimulus of ionomycin and phorbol 12-myristate 13-acetate. After fixation and permeabilization, cell samples were immunofluorescently stained for cell surface antigens (CD4 and CD8), intracellular interferon (IFN)-gamma, and interleukin (IL)-4 synthesis. Results were correlated with corresponding enzyme-linked immunosorbent assay measurements of the culture supernatants. MEASUREMENTS AND MAIN RESULTS: The phenotypic analysis of the composition of the helper (CD4) and suppressor/cytotoxic (CD8) T-cell subset demonstrated that patients suffering from major burns and healthy controls express these antigens in similar percentages. The ratio of CD4 positive to CD8 positive/CD16 negative T-cell subsets showed no significant changes after trauma compared with controls. The production of IL-4 was excessively up-regulated while the release of IFN-gamma was only slightly increased. The predominant cell source of IL-4 after burn trauma was the CD8+ cell with nearly five-fold increased production on day 5 (7.2+/-2.6%) vs. 1.5+/-0.4% in controls. While CD8+ cells are also capable of enhancing their IFN-gamma synthesis under stress by about 60% due to the significant participation of the naive CD45RA+ subset, the CD4+ IFN-gamma release remained largely unchanged. With this study, we demonstrated that in nonsurvivors the number of CD8+ IL-4-producing cells was significantly higher compared with controls; also, the number of IFN-gamma-releasing memory/effector CD45RO+ cells was lower compared with survivors. CONCLUSIONS: In previous experiments, we show that a shift to T(H)2 dominated phenotypes increases the risk for postburn infection. The current study confirms that major burns induce a significant shift of cytokine response in the T(H)2 direction and demonstrates that the CD8+, rather than the CD4+ phenotype, is present. Increased IL-4 production is associated with the T(H)2 lymphocyte. These diagnostic tests may help to differentiate patients with compensatory anti-inflammatory response syndrome and immunosuppression from those patients in the proinflammatory state associated with the systemic inflammatory response syndrome. The profile described in this article is associated with immunosuppression and may contraindicate attempts at anti-inflammatory therapy for sepsis.
Authors: Luis A Socha; John Gowardman; Diego Silva; Manuel Correcha; Nikolai Petrosky Journal: Intensive Care Med Date: 2006-01-26 Impact factor: 17.440
Authors: Paul Wurzer; Megan R Cole; Robert P Clayton; Gabriel Hundeshagen; Omar Nunez Lopez; Janos Cambiaso-Daniel; Raimund Winter; Ludwik K Branski; Hal K Hawkins; Celeste C Finnerty; David N Herndon; Jong O Lee Journal: Burns Date: 2017-04-15 Impact factor: 2.744
Authors: Alfred Ayala; Yanli Ding; Rebecca J Rhee; Lesley A Doughty; Patrician S Grutkoski; Chun-Shiang Chung Journal: Rec Res Dev Immunol Date: 2003-01-12
Authors: P G Boelens; J C M Fonk; A P J Houdijk; R J Scheper; H J T H M Haarman; S Meijer; P A M Van Leeuwen; B M E von Blomberg-van der Flier Journal: Clin Exp Immunol Date: 2004-05 Impact factor: 4.330
Authors: Chlodwig Kirchhoff; Peter Biberthaler; Wolf E Mutschler; Eugen Faist; Marianne Jochum; Siegfried Zedler Journal: Crit Care Date: 2009-06-11 Impact factor: 9.097