EFFECT OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AND SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR IN ANIMAL-MODELS OF INFECTION

Intracisternal or intraarticular inoculation of rabbit recombinant int erleukin (IL)-1 beta and rabbit tumor necrosis factor-alpha combined w ith IL-1 receptor antagonist (IL-1RA) and soluble tumor necrosis facto r receptor (sTNFR), respectively, produced significantly less inflamma tion in rabbits than after inoculation of these cytokines alone. In co ntrast, when Haemophilus influenzae type b (Hib) or Hib lipooligosacch aride (LOS) was given intraarticularly with IL-1RA, sTNFR, or the comb ination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation. In the experimen tal meningitis model, IL-1RA and sTNFR did not significantly reduce th e meningeal inflammatory response associated with intracisternal inocu lation of Hib LOS. These data indicate that specific cytokine inhibito rs (sTNFR and IL-1RA) may not be effective in modulating inflammation induced by a broad inflammatory stimulus such as gram-negative bacteri a or their products and suggest caution in using them to treat these i nfectious conditions in humans.