Combined inhibition of interleukin-1 and tumor necrosis factor in rodent endotoxemia: improved survival and organ function.

Abstract

The interleukin (IL)-1 receptor antagonist (Ra) and a polyethylene glycol-linked dimer of the type I soluble receptor of tumor necrosis factor (TNF), PEG-(rsTNF-RI)2, were used to determine whether maximal protection against lethality and organ dysfunction is achieved by single or dual cytokine inhibition under rigorous conditions of rodent endotoxemia. Inhibition of IL-1 or TNF alone protected maximally against lethality when inhibitors were given simultaneously with lipopolysaccharide (LPS) under minimal lethal conditions. Combined inhibition of IL-1 and TNF was necessary to maximally protect against lethality when treatment was delayed until 7 h after LPS injection under minimal lethal conditions or when treatment was begun immediately after LPS injection under supralethal conditions. Improved survival in IL-1Ra- plus PEG-(rsTNF-RI)2-treated rats was associated with enhanced protection against renal and metabolic dysfunctions. Thus, under very severe conditions of endotoxemia, TNF and IL-1 may act independently to mediate lethality and some organ dysfunctions.

• Authors: D A Russell, K K Tucker, N Chinookoswong, R C Thompson, T Kohno
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 171 Issue 6 Pg. 1528-38 (Jun 1995) ISSN: 0022-1899 [Print] United States
• PMID: 7769288 (Publication Type: Journal Article)

Chemical References

• Endotoxins
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1
• Lipopolysaccharides
• Receptors, Tumor Necrosis Factor
• Sialoglycoproteins
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Endotoxins (blood)
• Female
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1 (antagonists & inhibitors)
• Lipopolysaccharides (toxicity)
• Rats
• Rats, Inbred Lew
• Receptors, Tumor Necrosis Factor (antagonists & inhibitors, chemistry)
• Sialoglycoproteins (administration & dosage)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)