SUPPRESSION OF NATURAL-KILLER-CELL ACTIVITY IN PATIENTS WITH FRACTURESOFT-TISSUE INJURY

Background: Natural killer cells (NKCs) participate in ''innate'' cell -mediated immunity. Fracture/soft tissue injuries are cytokine rich an d may influence cell-mediated immunity. Objective: To study the effect s of fracture cytokines on NKC function. Design: A case-control study. Setting: A level I trauma center and laboratory in a university medic al center. Participants: Patients requiring open fracture fixation and healthy volunteers. Interventions: Fracture supernatants and peripher al plasma were collected during open fracture fixation. Volunteer mono nuclear cells were used as effector (NKC) sources. Mononuclear cells w ere preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions. Main Outcome Measures: Nat ural killer cell lysis of K562 target cells was assessed by chromium 5 1 release. Results: Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 day s after injury were most suppressive. Inactivation of complement and r eactive oxygen species failed to restore lysis. Neutralizing antibodie s to interleukin 4 and interleukin 10 further suppressed lysis. Antibo dies to transforming growth factor beta 1 failed to restore lysis. The addition of interferon gamma did not restore lysis but the addition o f interleukin 12 did. Conclusions: Fracture supernatants and periphera l plasma from patients with fractures suppress NKCs. The responsible m ediators may be concentrated in fracture/soft tissue injuries. Respons es to manipulation of the cytokine environment suggest that fracture c ytokines may impair cooperation between NE;Cs and accessory cells.