Interleukin-18 restores immune suppression in patients with nonseptic surgery, but not with sepsis

Background We investigated cellular immune responses, in particular interferon γ (IFN-γ) production, by peripheral blood mononuclear cells (PBMCs) in patients with septic and nonseptic surgical stress, focusing on interleukin (IL)-18 and its receptor (IL-18R). Methods Thirty-two patients with alimentary tract carcinoma who underwent elective surgery (OP) and 26 septic patients (SP) with peritonitis were enrolled in this study. Blood was collected on the first postoperative day (POD1), POD5, POD10, and POD15 in the OP group and on the emergency admission in the SP group. Ten healthy volunteers served as controls. PBMCs were cultured in the presence of anti-CD3 antibody or IL-2 and IL-12, with or without additional IL-18 stimulation, to measure IFN-γ production. IL-18R expression on CD56+NK (natural killer) cells was evaluated by flow cytometry. Results IL-2– and IL-12–induced IFN-γ production by PBMCs was suppressed significantly in both the OP (POD5) and SP groups compared with that in healthy controls. Interestingly, additional IL-18 stimulation up-regulated IFN-γ production by PBMCs in the OP group as well as the control group, but not in the SP group. IL-18R expression on CD56+NK cells was maintained consistently in the OP group as well as the control group, but decreased in the SP group. Conclusions IFN-γ production induced by cytokines (IL-2 and IL-12) was suppressed in PBMCs from both patients with sepsis and those who had undergone elective surgery. However, IL-18R expression on CD56+NK cells was different between patients with sepsis and nonseptic surgical stress. Our results suggest that exogenous IL-18 administration may be effective in preventing immune suppression in patients with nonseptic elective surgery.