Immunological status of septic and trauma patients. II. Proliferative response and production of interleukin 6 and tumor necrosis factor alpha by peripheral blood mononuclear cells from septic survivor, nonsurvivor and trauma patients: a correlation with the survival rate.

We have studied proliferative response to phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) of peripheral blood mononuclear cells (PBMC) and their ability to produce IL-6 and TNF-alpha in vitro in: septic survivors, nonsurvivors and with multiple injury patients. Blood samples for determination of PBMC reactivity were taken upon admission and after 1, 2 and 5 days later. The proliferative response of lymphocytes, both spontaneous as well as PHA- and LPS-induced, was generally higher in septic nonsurvivor patients comparing to other groups. Markedly elevated LPS-induced proliferation (particularly on day 3) was a bad prognostic sign for survival. The ability of PBMC from the patients to produce IL-6 in culture was depressed in nonsurvivor septic patients and elevated in trauma patients, comparing to control donors. More profound differences were found with respect to TNF-alpha production which was deeply depressed (both spontaneous and induced) in septic nonsurvivors. In contrast, TNF-alpha production in septic survivors was significantly higher with a peak response on day 3. Trauma patients, on the other hand, had significantly increased ability to produce TNF-alpha on day 1 and 2, declining thereafter. The data presented in this report reveal that low production (or even anergy) with respect to synthesis of proinflammatory cytokines in vitro, as well as increased spontaneous proliferation of PBMC and proliferation in response to LPS, are significantly correlated with the fatal outcome of the septic shock.