Pharmacodynamic effects of the murine p75-Fc fusion protein in mice.
Overproduction of inflammatory mediators, such as tumor necrosis factor (TNF), is key to the development and maintenance of inflammatory processes. Etanercept is a soluble TNF receptor fusion protein used in the treatment of various chronic inflammatory diseases, including rheumatoid arthritis and psoriasis. This study investigated the effects of murine p75-Fc, a soluble TNF receptor protein, on TNF-induced IL-6 production in mice. Six groups of mice received either murine p75-Fc (0.15, 0.50, 1.5, 5, and 15 mg/kg) or phosphate-buffered saline. Three days later, mice were injected intravenously with 10 microg of murine TNF and blood samples were taken after 3 hours. Serum IL-6 and TNF were measured by ELISA. Mice treated with 5 and 15 mg/kg murine p75-Fc demonstrated complete inhibition of TNF-induced IL-6 production. Murine p75-Fc (1.5 mg/kg) resulted in a partial but significant reduction of TNF-induced IL-6 production. No TNF was detected in 5 and 15 mg/kg murine p75-Fc-treated mice, except one in the 5 mg/kg dose group. In conclusion, murine p75-Fc completely inhibits TNF-induced IL-6 production in mice.
Hu
Yi-Ling
YL
Amgen Inc, Thousand Oaks, California 91320-1799, USA.
Kim
Helen Y
HY
Kohno
Tadahiko
T
Khare
Sanjay D
SD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept