December 1997

Suppression of Natural Killer Cell Activity in Patients With Fracture/Soft Tissue Injury

Author Affiliations

From the Departments of Surgery, UMDNJ—New Jersey Medical School, Newark (Drs Hauser and Livingston and Mr Lavery); and the University of Mississippi Medical Center, Jackson (Drs Joshi and Zhou and Mr Jones).

Arch Surg. 1997;132(12):1326-1330. doi:10.1001/archsurg.1997.01430360072013

Background:  Natural killer cells (NKCs) participate in "innate" cell-mediated immunity. Fracture/soft tissue injuries are cytokine rich and may influence cell-mediated immunity.

Objective:  To study the effects of fracture cytokines on NKC function.

Design:  A case-control study.

Setting:  A level I trauma center and laboratory in a university medical center.

Participants:  Patients requiring open fracture fixation and healthy volunteers.

Interventions:  Fracture supernatants and peripheral plasma were collected during open fracture fixation. Volunteer mononuclear cells were used as effector (NKC) sources. Mononuclear cells were preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions.

Main Outcome Measures:  Natural killer cell lysis of K562 target cells was assessed by chromium 51 release.

Results:  Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 days after injury were most suppressive. Inactivation of complement and reactive oxygen species failed to restore lysis. Neutralizing antibodies to interleukin 4 and interleukin 10 further suppressed lysis. Antibodies to transforming growth factor β1 failed to restore lysis. The addition of interferon γ did not restore lysis but the addition of interleukin 12 did.

Conclusions:  Fracture supernatants and peripheral plasma from patients with fractures suppress NKCs. The responsible mediators may be concentrated in fracture/ soft tissue injuries. Responses to manipulation of the cytokine environment suggest that fracture cytokines may impair cooperation between NKCs and accessory cells.Arch Surg. 1997;132:1326-1330