Elevated Tumor Necrosis Factorα Production Concomitant to Elevated Prostaglandin E2 Production by Trauma Patients' Monocytes

Abstract

• The level of tumor necrosis factor_α(TNF_α), a monokine implicated in mediating septic shock, is elevated in the blood of some patients with sepsis. Monocytes from 11 trauma patients and 11 burn patients were suboptimally stimulated with interferon gamma and muramyl dipeptide, an analogue of bacterial wall products. The patients with sepsis showed significantly greater total TNF_αlevels (secreted in combination with cell-associated) 3 days before septic episodes, as compared with normal controls (32.38 to 2231.76 ng/10⁶monocytes per milliliter, median = 121.03 ng/10⁶monocytes per milliliter; normal control: 0.00 to 18.20 ng/10⁶monocytes per milliliter, median = 5.93 ng/10⁶monocytes per milliliter). Increases in patients' total monocyte TNF_αlevels greater than 30 ng/10⁶monocytes per milliliter correlated with septic episodes. In patients with sepsis, the total monocyte TNF_levels were increased despite a concomitant increase in their prostaglandin E₂levels in both stimulated (interferon gamma plus muramyl dipeptide) and unstimulated in vitro assays (9 patients: stimulated prostaglandin E₂range, 30.1 to 123.6 ng/10⁶monocytes per milliliter). Massively elevated monocyte TNF_αand prostaglandin E₂production occurred simultaneously in patients with sepsis. (Arch Surg.1990;125:29-35)