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R Neta, SN Vogel, JM Plocinski, NS Tare, W Benjamin, R Chizzonite and M Pilcher
Department of Experimental Hematology, Armed Forces Radiobiology Research
Institute, Bethesda, MD.
Interleukin-1 (IL-1) is radioprotective and induces both circulating
colony-stimulating factor(s) (CSF) and IL-6 in mice. We evaluated the
relationship among these three responses to IL-1 using anti-IL-1 receptor
antibody 35F5. This antibody in vitro blocks responses of T cells and
fibroblasts, but not of B cells or myeloid cell lines, to IL- 1.
Administration of 35F5 alone before irradiation reduced the number of
surviving mice compared with those not treated with 35F5, demonstrating
that endogenous IL-1 participates in the natural resistance to radiation.
Thirty micrograms of 35F5 per mouse also reduced by 92% the survival of
irradiated mice pretreated with 0.3 micrograms of IL-1. Similarly, 30
micrograms of 35F5 reduced by 96% to 98% the induction of IL-6 by IL-1. In
contrast, 30 micrograms of 35F5 resulted in only moderate reduction of
circulating CSF. Consequently, the level of circulating CSF after 35F5
treatment was still equivalent to levels of CSF that were induced by doses
of IL-1 in the radioprotective range. Because treatment with 35F5 antibody
resulted in the blocking of IL-1-reduced radioprotection, the above results
suggest that circulating CSF, by itself, may not be sufficient for
radioprotection. This conclusion supports our previous results which showed
that granulocyte-macrophage CSF (GM-CSF) and G-CSF were radioprotective
only when administered with suboptimal doses of IL-1.
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