Suppression of natural killer cell activity in patients with fracture/soft tissue injury.
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.


METHODS
A case-control study.


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


METHODS
Patients requiring open fracture fixation and healthy volunteers.


METHODS
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.


METHODS
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 beta1 failed to restore lysis. The addition of interferon gamma 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.
Hauser
C J
CJ
Department of Surgery, UMDNJ-New Jersey Medical School, Newark 07103-2714, USA. hausercj@umdnj.edu
Joshi
P
P
Jones
Q
Q
Zhou
X
X
Livingston
D H
DH
Lavery
R F
RF
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology; D005264:Femoral Fractures / Q000276:immunology; D005596:Fractures, Closed / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008875:Middle Aged; D010384:Pelvic Bones / Q000293:injuries; D017695:Soft Tissue Injuries / Q000276:immunology*; D013978:Tibial Fractures / Q000276:immunology
D016207:Cytokines