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Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha tumor necrosis factor alpha granulocyte colony stimulating factor and murine recombinant granulocyte macrophage colony stimulating factor



Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha tumor necrosis factor alpha granulocyte colony stimulating factor and murine recombinant granulocyte macrophage colony stimulating factor



Journal of Immunology 140(1): 108-111



Interleukin 1.alpha. (IL-1.alpha.), tumor necrosis factor .alpha. (TNF.alpha.), granulocyte-colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) are molecularly distinct cytokines acting on separate receptors. The release of these cytokines can be concomitantly induced by the same signal and from the same cellular source, suggesting that they may cooperate. Administered alone, human recombinant (hr)IL-1.alpha. and hrTNF.alpha. protect lethally irradiated mice from death, whereas murine recombinant GM-CSF and hrG-CSF do not confer similar protection. On a dose basis, IL-1.alpha. is a more efficient radioprotector than TNF.alpha. At optimal doses, IL-1.alpha. is a more radioprotective cytokine than TNF.alpha. in C57BL/6 and B6D2F1 mice and less effective than TNF.alpha. in C3H/HeN mice, suggesting that the relative effectiveness of TNF.alpha. and IL-1.alpha. depends on the genetic makeup of the host. Administration of the two cytokines in combination results in additive radioprotection in all three strains. This suggests that the two cytokines act through different radioprotective pathways and argues against their apparent redundancy. Suboptimal, nonradioprotective doses of IL-1.alpha. also synergize with GM-CSF or G-CSF to confer optimal radioprotection, suggesting that such an interaction may be necessary for radioprotection of hemopoietic progenitor cells.

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Accession: 005728528

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PMID: 2447166


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