CYTOKINE-ASSOCIATED TISSUE-INJURY AND LETHALITY IN MICE - A COMPARATIVE-STUDY

A comparative study was performed to examine the lethal effects of several cytokines injected into mice sensitized with actinomycin D (Act-D). Consistent with published data, human tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (0.2-5 μg) caused the death of the animals within 8-12 hr after injection. Human interleukin-6 (IL-6) and interleukin-8 (IL-8) (0.6-6 μg) known to be induced by TNF-α did not show any lethal effects, indicating that TNF-α-associated lethality is not mediated by IL-6 or IL-8. Human tumor necrosis factor-β (TNF-β) (also called lymphotoxin), which shares structural and functional properties with TNF-α, was as potent as TNF-α in its lethal effects. Murine interferon-γ (IFN-γ) (0.04-5 μg) was also tested and showed no lethal effects in this model. In addition, a synthetic peptide corresponding to amino acid residues 163-171 of IL-1β, and which has been shown to lack the inflammatory effects of IL-1β, also caused no lethality among Act-D sensitized mice. The pretreatment of mice with IL-6, IL-8, or IFN-γ had no protective effects on TNF-α or IL-1β-induced lethality in contrast to the protection observed by a pretreatment with TNF-α/IL-1β themselves or with endotoxin. Histopathologic data showed that severe tissue injury in vital organs is associated with the rapid lethality among sensitized mice. © 1991 Academic Press, Inc.