Monocyte Deactivation and Altered T Helper Lymphocyte Phenotype in Septic and Traumatic Patients

Abstract

In an effort to assess surgical stress by means of the immune response, we focused on the T cell secretion of cytokines that regulate the critical balance of either T helper type-1 (Th1)-or Th2-mediated immune response on pro- and anti-inflammatory activities. We also measured histocompatibility leukocyte antigen (HLA)-DR expression and cytokine synthesis in peripheral blood monocytes. The patients admitted to our ICU between June 2000 and December 2002 were recruited for this study. In a prospective study, 6 septic patients, 5 patients with burn injury, 9 trauma patients and 6 healthy control subjects were included. Peripheral blood mononuclear cells (PBMCs) from each subject were isolated and stimulated with lipopolysaccharide, and phorbol myristate acetate plus ionomycin. Cell surface marker expression (CD4, CD14, and HLA-DR) and in vitro intracytoplasmic cytokine production (IL-1, IL-1ra, TNF, IL-10, IL-6, IL-4, and IFN-γ) were measured by flow cytometry. The frequency of IFN-γ-producing Th1 cells from burn (9.4±8.1, p<0.05), trauma (injury severity score±25)(11.3±7.5, p<0.05) and septic (6.2±2.3, p<0.01) patients was significantly decreased when compared with the healthy individuals (23.1±8.1). The frequency of IL-4-producing Th2 cells remained largely unchanged in all groups. Monocyte HLA-DR expression also was decreased in traumatic, septic and burn patients. Septic and traumatic patients showed significant suppression of Th1 cytokine production concomitant with the decrease in monocyte HLA-DR expression. The results therefore suggest that downregulation of Th1 cell-mediated immune response and monocyte deactivation defined as immunoparalysis may be an important mechanisms of immunosuppression observed after surgical stress and may contribute to increased susceptibility to infectious complication.