Critically ill patients are at risk for
sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete
interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early
sepsis compared with postoperative patients. IFNγ secretion [
enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV),
pokeweed mitogen (PWM), muromonab-anti-CD3 (
OKT3), and
human leukocyte antigen (
HLA)-DRA-
mRNA expression and serum
cytokine concentrations were repeatedly [days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with
sepsis (n = 7) and patients undergoing major abdominal surgery (radical
prostatectomy,
cystectomy, n = 10). In a second cohort,
HLA-DRA expression was assessed in 80 patients with
sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with
sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV (P = 0.01),
OKT3 (P = 0.02), and PWM (P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ.
HLA-DRA expression was also significantly decreased in patients with
sepsis at all time points (P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and
OKT3 as well as
HLA-DRA expression was already decreased upon ICU admission in patients with
sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with
sepsis.NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and
pokeweed mitogen in mononuclear blood cells of patients with early
sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in
sepsis.
Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with
sepsis.