T-cell reactivity and its predictive role in immunosuppression after burns

Objective: To obtain further insight into the constitutional, phenotype-dep endent 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 h ealthy individuals. Interventions: Peripheral blood mononuclear cells were separated rated and incubated (5 hrs) for cytokine production induced by the accessory cell-ind ependent stimulus of ionomycin and phorbol 12-myristate 13-acetate. After f ixation and permeabilization, cell samples were immunofluorescently stained for cell surface antigens (CD4 and CD8), intracellular interferon (IFN)-ga mma, and interleukin (IL)-4 synthesis. Results were correlated with corresp onding en zyme-linked immunosorbent assay measurements of the culture super natants. Measurements and Main Results: The phenotypic analysis of the composition o f the helper (CD4) and suppressor/cytotoxic (CD8) T-cell subset demonstrate d that patients suffering from major burns and healthy controls express the se antigens in similar percentages. The ratio of CD4 positive to CD8 positi ve/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 predominan t 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 contr ols. While CD8+ cells are also capable of enhancing their IFN-gamma synthes is under stress by about 60% due to the significant participation of the na ive 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, t he number of IFN-gamma-releasing memory/effector CD45RO+ cells was lower co mpared with survivors. Conclusions: In previous experiments, we show that a shift to T(H)2 dominat ed phenotypes increases the risk for postburn infection. The current study confirms that major burns induce a significant shift of cytokine response i n the T(H)2 direction and demonstrates that the CD9+, rather than the CD4phenotype, is present. Increased IL-4 production is associated with the T(H )2 lymphocyte. These diagnostic tests may help to differentiate patients wi th compensatory anti inflammatory response syndrome and immonosup pression from those patients in the proinflammatory state associated with the system ic inflammatory response syndrome. The profile described in this article is associated with immunosuppression and may contraindicate attempts at anti- inflammatory therapy for sepsis.