Effect of interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor in animal models of infection

Intracisternal or intraarticular inoculation of rabbit recombinant interleukin (IL)-β and rabbit tumor necrosis factor-α combined with IL-l receptor antagonist (IL-l RA) and soluble tumor necrosis factor receptor (sTNFR), respectively, produced significantly less inflammation in rabbits than after inoculation of these cytokines alone. In contrast, when Haemophilus influenzae type b (Rib) or Rib lipooligosaccharide (LOS) was given intraarticularly with IL-lRA, sTNFR, or the combination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation. In the experimental meningitis model, IL-IRA and sTNFR did not significantly reduce the meningeal inflammatory response associated with intracisternal inoculation of Rib LOS. These data indicate that specific cytokine inhibitors (sTNFR and IL-lRA) may not be effective in modulating inflammation induced by a broad inflammatory stimulus such as gram-negative bacteria or their products and suggest caution in using them to treat these infectious conditions in humans.