Tumor necrosis factor antibody treatment of septic baboons reduces the production of sustained T-cell suppressive factors.
Post-traumatic septic complications result from impaired cell-mediated immune function, which is caused in part by circulating T-cell suppressive factors (TSFs). We examined whether tumor necrosis factor alpha (TNF-alpha) antibody treatment in a baboon sepsis model influences the production of TSFs, including interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Sepsis was induced in anesthetized baboons by Escherichia coli infusion, and caused an increase in plasma levels of TNF, TSF activity, IL-10, and active TGF-beta, as well as a decrease in latent TGF-beta. TNF antibody pretreatment reduced TNF levels by 98%. Transient TSF activity (0-4 h) was only marginally influenced, while sustained TSF activity (8-24 h) was markedly reduced. TSF activity at 24 h correlated with peak TNF levels. IL-10 levels, coinciding with early TSF activity, remained unchanged by anti-TNF treatment. Levels of active TGF-beta and the drop in latent TGF-beta were decreased. We conclude that anti-TNF treatment reduces sustained TSF activity and may partially restore impaired cell-mediated immune function.
Junger
W G
WG
Department of Surgery, University of California San Diego 92103, USA.
Hoyt
D B
DB
Redl
H
H
Liu
F C
FC
Loomis
W H
WH
Davies
J
J
Schlag
G
G
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D010215:Papio; D018805:Sepsis / Q000276:immunology* / Q000628:therapy*; D013491:Suppressor Factors, Immunologic / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000906:Antibodies; D006133:Growth Substances; D008070:Lipopolysaccharides; D013491:Suppressor Factors, Immunologic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10