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)-1 beta and rabbit tumor necrosis factor-alpha combined with IL-1 receptor antagonist (IL-1RA) 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 (Hib) or Hib lipooligosaccharide (LOS) was given intraarticularly with IL-1RA, sTNFR, or the combination, there was no significant or consistent modulation of synovial inflammation and cartilage proteoglycan degradation. In the experimental meningitis model, IL-1RA and sTNFR did not significantly reduce the meningeal inflammatory response associated with intracisternal inoculation of Hib LOS. These data indicate that specific cytokine inhibitors (sTNFR and IL-1RA) 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.
París
M M
MM
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
Friedland
I R
IR
Ehrett
S
S
Hickey
S M
SM
Olsen
K D
KD
Hansen
E
E
Thonar
E J
EJ
McCracken
G H
GH
D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy*; D001929:Brain Edema / Q000188:drug therapy; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D006192:Haemophilus Infections / Q000188:drug therapy*; D006193:Haemophilus influenzae; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D007632:Keratan Sulfate / Q000032:analysis; D007773:Lactates / Q000134:cerebrospinal fluid; D019344:Lactic Acid; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008583:Meningitis, Haemophilus / Q000188:drug therapy*; D011817:Rabbits; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins / Q000627:therapeutic use*; D012995:Solubility; D013582:Synovial Fluid / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002556:Cerebrospinal Fluid Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007773:Lactates; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D007632:Keratan Sulfate