Cytokine-associated tissue injury and lethality in mice: A comparative study

doi:10.1016/S0090-1229(06)80008-5

Clinical Immunology and Immunopathology

Volume 61, Issue 1, October 1991, Pages 69-82

https://doi.org/10.1016/S0090-1229(06)80008-5 Get rights and content

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.

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Cytokine-associated tissue injury and lethality in mice: A comparative study

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Clin. Immunol. Immunopathol.

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Lab. Invest.

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Cancer Res.

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J. Clin. Oncol.

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J. Immunol.

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Nature

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