Differential sensitivity of in vivo TNF and IL-6 production to modulation by anti-inflammatory drugs in mice.

The effect of dexamethasone and two non-steroidal anti-inflammatory agents ibuprofen and indomethacin on the production of serum interleukin 6(IL-6) and tumor necrosis factor (TNF) levels in mice treated with endotoxin (2.5 micrograms/mouse, i.p.) was investigated. Pretreatment of mice with dexamethasone (0.3-30.0 mg/kg, i.p., 30 min before endotoxin) completely blocked TNF production but did not affect that of IL-6. Conversely, pretreatment with indomethacin (5 mg/kg, i.p.) or ibuprofen (30 mg/kg, i.p.) potentiated the production of both IL-6 (+ 80% with INDO; + 100% with IBU) and TNF (+ 500% with INDO; + 50% with IBU). In the case of IL-6, the two anti-inflammatory drugs were able per se to induce significant levels of this cytokine even in the absence of LPS. These data indicate that IL-6 and TNF production are differently susceptible to glucocorticoids, and that prostaglandins can physiologically provide a negative feedback regulation of IL-6 and TNF synthesis.