Alteration of Monocyte Function Following Major Injury

Abstract

• The macrophage exerts its stimulatory and regulatory functions within the specific immune response via the interleukin 1 (IL-1) and prostaglandin E₂ (PGE₂), respectively. In a screening study of macrophage-related variables following injury, a total of 58 patients (mean age, 32 years; mean Injury Severity Score, 38), macrophagic phenotyping with the monoclonal antibody Leu M3 and serial measuring of the antagonistic monokines IL-1 and PGE₂ and of the macrophage-activating lymphokine interferon gamma were carried out on posttrauma days 0,1,3,5,7,10,14, and 21. The posttraumatic course was characterized by significant monocytosis, showing a peak value of 32% of Leu M3—positive cells compared with 15% of these cells in normal control subjects. During the posttrauma course, the macrophagic PGE₂ output was significantly elevated up to eightfold on days 5 and 7 compared with that of control subjects (0.441 ±0.14 ng/mL vs 0.052 ± 0.01 ng/mL). Conversely, macrophagic IL-1 synthesis was significantly suppressed until day 10. Levels of interferon gamma were suppressed to a significant degree during the two-day observation period, with a trend to slow recovery at the end of week 3. These data suggest that a negative regulatory macrophagic function may be the event initiating posttraumatic immunosuppression. To restore impaired macrophagic T-helper cell interaction, cyclo-oxygenase inhibition and substitution of interferon gamma may be useful to potentiate facilitatory macrophagic function and to block inhibitory macrophagic activity. (Arch Surg 1988;123:287-292)