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: 2.6 ± 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⁺: 6.5 ± 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.