Down regulation of monocyte antigen presentation in critical illness and septic shock

Introduction: Monocyte HLA-DR expression is decreased in sepsis. However, antigen presentation and the expression of other costimulatory molecules have not been studied in this setting. Methods: We examined antigen presentation (Antig P) using in vitro lymphocyte response to tuberculin toxoid. Lymphocyte incorporation of 5-bromo-2-deoxyuridine was measured by ELISA as % absorbance (% abs). Ten normal controls, 10 critically ill non-septic patients (CINS), 15 patients with septic shock (SS) were studied. Monocyte (M) HLA-DR and CD-86 receptors was evaluated by flow cytometry as were lymphocyte (L) expression of CD28 and CTLA. Flow cytometry data are presented as % expression. All data are presented as mean ± SE.*P<0.5 vs control. + p<005 vs CINS. Results: C CINS SS AGE(yrs) 57±7 65±7 68±6 APACHE III - 51±4 88±12+ Antig P (% abs) 989±313 235±65*111±55*M-HLA-DR (%) 81±5 57±11 47±6*M-CD-86(%) 69±5 34±8*22±3.6*L-CTLA (%) 0.1±0.1 0.3±0.2 1±0.4*L-CD28 (%) 62±3 56±5 35±7*+ Conclusion: Antigen presentation is decreased in SS and critical illness. The decrease appears greater in SS and is associated with significant decreases in HLA-DR expression and the expression of other monocyte (CD-86) and lymphocyte (CD28) costimulatory molecules. Increased expression of the negative lymphocyte signal receptor (CTLA) is also present in SS and may contribute to decreased antigen presentation.