Role of elevated monocyte transforming growth factor beta (TGF beta) production in posttrauma immunosuppression

We previously reported that increased production of prostaglandin E2 by monocytes is a pivotal mechanism in posttrauma immunopathology. Here we characterize monocyte levels of transforming growth factor beta and examine the effects of elevated transforming growth factor beta on prostaglandin E2 release by patients' monocytes. Trauma patients' and normals' monocyte supernates (+/- stimulation with muramyl dipeptide) were acid treated and assayed for transforming growth factor beta using the mink lung-cell bioassay. Alternatively, human transforming growth factor beta was added to patients' and normals' monocytes and prostaglandin E2 production assayed. Significantly elevated transforming growth factor beta levels (median = 181.7 pmol/10(6) monocytes) were detected in immunosuppressed patients' monocytes but not immunocompetent trauma patients' (median = 32.0 pM) or normals' (median = 20.4 pM) monocytes. Adding transforming growth factor beta to monocytes resulted in a significant elevation of prostaglandin E2 levels. Elevated monocyte transforming growth factor beta levels in trauma patients could be both suppressing T-lymphocyte functions and maintaining elevated monocyte prostaglandin E2 synthesis.