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  • Title: Inhibition of tumor necrosis factor production by lymphocytes from anti-TNF antibody-treated, cardiac-allografted rats.
    Author: Wei RQ, Lin H, Chen GH, Beer DG, Kunkel SL, Bolling SF.
    Journal: J Surg Res; 1994 Jun; 56(6):601-5. PubMed ID: 8015317.
    Abstract:
    Tumor necrosis factor-alpha (TNF) is a multifunctional cytokine involved in the immunopathologic consequences of allograft rejection. We have previously demonstrated that anti-TNF antibody treatment prolongs cardiac allograft survival in rats. To elucidate the mechanism of anti-TNF antibody in modulating the immune response, we investigated TNF production by spleen and lymph node cells from anti-TNF antibody-treated Lewis rats who received MHC-mismatched Brown Norway rat cardiac allografts. In 10 untreated rats, cardiac allografts were rejected at 6.8 +/- 0.6 days after transplantation (mean +/- SD). Anti-TNF antibody treatment enhanced graft survival to 12.7 +/- 1.4 days (P < 0.001 vs controls). In other anti-TNF antibody-treated recipients spleen and lymph node cells were isolated on Day 5 after transplant. TNF production was measured and showed significantly less TNF than those from untreated (no anti-TNF antibody), transplanted recipient rats (28.7 u/10(6) spleen cells vs 76.4 u/10(6) spleen cells at 2 hr and 4.6 u/10(6) lymph node cells vs 9.2 u/10(6) lymph node cells at 24 hr). Furthermore, following lipopolysaccharide stimulation, spleen cells from anti-TNF-treated rats again produced significantly less TNF than those from untreated transplanted rats (68.9 u/10(6) cells vs 189.4 u/10(6) cells at 2 hr). Finally, with allogeneic cell stimulation, anti-TNF treated rats again produced significantly less TNF than untreated transplanted rats (spleen cells, 2.2 u/10(6) cells vs 40.4 u/10(6) cells at 24 hr; lymph node cells, 1.2 u/10(6) cells vs 22.2 u/10(6) cells at 72 hr). These findings suggest that anti-TNF antibody treatment may not only neutralize TNF activity, but also suppress TNF production itself, providing a new insight into the regulation of TNF by anti-TNF antibody.
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