Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients

Anti-inflammatory substances are released during septic shock that modulate monocyte function. Decreased monocyte responsiveness to bacterial toxins a nd decreased expression of human-leukocyte-associated antigen-DR (HLA-DR) h ave been reported during septic shock and critical illness. Impaired antige n presentation has been inferred from these observations but has not been d emonstrated. We assessed antigen presentation and costimulatory molecule ex pression in 12 age-matched control subjects, 10 noninfected critically ill patients (CINS), and 17 critically ill patients with sepsis (CIS). Antigen presentation was assessed by using in vitro lymphocyte 5-bromo-2-deoxyuridi ne (BrdU) incorporation in response to tetanus toroid. The expression of HL A-DR and the costimulatory molecules CD28, CD86, and CTLA-4 was assessed by flow cytometry Serum interleukin-10 (IL-10) was also measured by enzyme-li nked immunosorbent assay. Serum IL-10 levels were significantly elevated in CIS patients (91 +/- 38 pg/ml) as compared with levels in control subjects (5 +/- 4 pg/mL)(P <.05). Lymphocyte BrdU incorporation increased by 710% /- 243% in control subjects but by only 144% +/- 62% in CIS patients and 76 % +/- 31% in CINS patients (P <.01 vs control). Monocyte HLA-DR expression, monocyte CD86 expression, and lymphocyte CD28 expression were significantl y decreased in CIS patients (P <.01) as compared with control subjects. Con versely, lymphocyte CTLA-4 expression was significantly increased in CIS pa tients (P <.05 vs control). Monocyte CD86 expression was also significantly decreased in CINS patients as compared with control subjects. These data i ndicate that antigen presentation is decreased in critically ill patients w ith sepsis, This appears in part related to decreased expression of HLA-DR and the costimulatory molecules CD86 and CD28, Increased expression of the negative signal receptor CTLA-4 may also impair antigen presentation in pat ients with sepsis.