Differential expression of tumor necrosis factor receptor subtypes on leukocytes in systemic inflammatory response syndrome

Objective: To determine the expression of tumor necrosis factor (TNF) receptor in patients with systemic inflammatory response syndrome (SIRS). Design: Prospective study. Setting: Intensive care unit and central laboratory. Patients: Blood specimens from 18 healthy volunteers (controls) and 16 patients with SIRS, Interventions: None. Measurements and Main Results: Using monoclonal antibodies, fluorescence labeling, and high sensitivity flow cytometry, we measured the expression of membrane TNF receptor subtypes TNF-R55 and TNF-R75 on peripheral blood leukocytes. Receptor expression is expressed as mean fluorescence intensity +/- SD (units: detection channel number). In controls, TNF-R55 was only weakly expressed (monocytes: 2.5+/-1.8; neutrophils: 0.7+/-0.8), whereas expression of TNF-R75 was higher (monocytes: 28.6 +/- 9.0; neutrophils: 4.8 +/- 1.0) and was also found on lymphocytes (on CD8(+) lymphocytes: 5.7 +/- 1.8; CD16(+): 5.5 +/- 1.2; CD4(+): 9.7 +/- 3.7), In SIRS, we observed increased expression of TNF-R55 on monocytes (6.9 +/- 3,4, p <.001) and neutrophils (2.2 +/- 1.9, p <.01), as well as decreased expression of TNF-R75 on monocytes (17.3 +/- 13.2; p <.001). The extent of TNF-R55 up-regulation did not correlate with that of TNF-R75 down-regulation. TNF-R55 on monocytes and neutrophils strongly correlated with body temperature but not with survival, whereas monocyte TNF-R75 was considerably lower in nonsurvivors, albeit not significantly (12.3 +/- 7.1 vs. 23.9 +/- 16.7; p=.07). Conclusions: These data indicate that leukocyte TNF-R55 and TNF-R75 react differentially and probably serve different functions in SIRS, which prompts the investigation of receptor subtype specific therapeutic approaches.