Tumor necrosis factor alpha regulation of immunoglobulin secretion in trauma patients.
Major trauma-related immune dysfunction is observed at the time of augmented release of immunopathologic mediators. In the present study, T cell-dependent immunoglobulin (Ig) synthesis in peripheral blood mononuclear cell (PBMC) cultures from blunt trauma patients (N = 12, injury severity score (ISS) 27-50), was reduced by 30- > 90%. This coincided with significantly (P < 0.001-0.01) elevated secretion of the biologically 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 increased (up to 300%) in cultures treated with 0.5-2 micrograms/ml of the antibody, where low levels of TNF alpha activity often persisted. However, immunoglobulin synthesis was eradicated in preparations exposed to higher concentrations (10 micrograms/ml) of anti-TNF alpha Ab and devoid of TNF alpha biological activity. The treatment with anti-TNF alpha Ab had no effect 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 function. Immunoregulatory potential of TNF alpha should, therefore, be considered in therapeutic strategies to abrogate its activity.
Teodorczyk-Injeyan
J A
JA
Department of Surgery, University of Toronto, Ontario, Canada.
Cembrzynska-Nowak
M
M
Lalani
S
S
Rizoli
S
S
Taylor
G
G
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014947:Wounds and Injuries / Q000276:immunology*
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens; D014409:Tumor Necrosis Factor-alpha