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  • Title: Recombinant IL-1 receptor antagonist protects against TNF-induced lethality in mice.
    Author: Everaerdt B, Brouckaert P, Fiers W.
    Journal: J Immunol; 1994 May 15; 152(10):5041-9. PubMed ID: 8176222.
    Abstract:
    The possible role of induced IL-1 in a number of in vivo actions of TNF was investigated. We were particularly interested to know whether a species-specific induction of IL-1 might explain the important differences observed between murine TNF and human TNF in systems such as lethal shock and the induction of long lasting, high levels of circulating IL-6 in mice. We also studied the possible involvement of IL-1 in the sensitization to TNF observed in tumor-bearing mice or in combination with D(+)-galactosamine or RU38486, particularly because such sensitization results in the loss of species-specific differences between both TNF. Using a specific rIL-1R antagonist (IL-1ra), which inhibits the binding of IL-1 to the IL-1R type I, we were able to protect mice against a lethal murine TNF injection. However, the induction of high levels of circulating IL-6 by murine TNF was not affected, although IL-1ra almost completely blocked the induction of IL-6 by exogenously administered IL-1. Furthermore, the increased susceptibility of tumor-bearing mice to human TNF, relative to control mice, or the sensitization by co-administration of RU38486 or D(+)-galactosamine do not seem to be mediated by IL-1.
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