J. Manjuck et al., Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients, J LA CL MED, 135(2), 2000, pp. 153-160
Citations number
35
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
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.