TUMOR-NECROSIS-FACTOR-ALPHA REGULATION OF IMMUNOGLOBULIN SECRETION INTRAUMA PATIENTS

Major trauma-related immune dysfunction is observed at the time of aug mented release of immunopathologic mediators. In the present study, T cell-dependent immunoglobulin (Ig) synthesis in peripheral blood monon uclear cell (PBMC) cultures from blunt trauma patients (N = 12, injury severity score (ISS) 27-50), was reduced by 30->90%. This coincided w ith significantly (P < 0.001-0.01) elevated secretion of the biologica lly active tumor necrosis factor alpha (TNF alpha). Modulation of the TNF alpha activity by anti-TNF alpha antibody (anti-TNF alpha Ab) led to dose-dependent alterations in IgG synthesis. IgG production increas ed (up to 300%) in cultures treated with 0.5-2 mu g/ml of the antibody , where low levels of TNF alpha activity often persisted. However, imm unoglobulin synthesis was eradicated in preparations exposed to higher concentrations (10 mu g/ml) of anti-TNF alpha Ab and devoid of TNF al pha biological activity. The treatment with anti-TNF alpha Ab had no e ffect on mitogen- or alloantigen-induced PBMC proliferation. Thus, in severely traumatized patients, biological activities of endogenous TNF alpha may include modulation of T cell-dependent B lymphocyte functio n. Immunoregulatory potential of TNF alpha should, therefore, be consi dered in therapeutic strategies to abrogate its activity. (C) 1994 Wil ey-Liss, Inc.