Mechanism of suppression of natural killer cell activity in trauma patients

Trauma patients develop a severe immunosuppression that includes suppressio n of natural killer (NK) cell activity although numbers of NK cells are not reduced. The mechanism of suppression of NK cell activity after major trau ma is not known. The aim of the present study was to investigate the in vit ro effect of plasma samples from trauma patients (TP) on the cytotoxic acti vity of normal NK cells. Buffycoat mononuclear cells (5 x 10(5)/well) were preincubated with either TP or plasma samples from age and sex matched heal thy controls (CP) for 0, 16 or 40 h. These effector cells were then culture d with Cr-51 labeled K-562 cells (2 x 10(4)/well) for 4 h at 37 degrees C a nd % lysis was calculated. No significant differences in % lysis between CP and TP were found with 0 or 16 h preincubation, however 40 h preincubation with TP severely suppressed NK cell function (p = 0.003) as compared to pr eincubation with CP for the same period. Addition of neutralizing anti-IL-4 , anti-TGF-beta 1, or anti-IL-10 antibodies did not reverse the NK cell sup pression. There was a partial reversal of NK cell suppression by catalase b ut not by SOD or L-NMMA. Removal of monocytes from buffycoat mononuclear ce lls also significantly reversed the NK cell suppression. These data suggest that suppression of NK cell activity in trauma patients may be an accessor y cell dependent phenomenon and may partially depend on production of react ive oxygen metabolites (ROM).