Comparison of in vivo effects of human recombinant IL 1 and human recombinant IL 6 in mice.
IL 1 and IL 6 share a number of biological activities, including induction of fever, neutrophilia and acute phase response, and IL 1 induces IL 6 production by fibroblasts and macrophages. Therefore, it was proposed that IL 6 mediates many of the activities of IL 1. To test this hypothesis in vivo, we assessed induction of IL 6 following IL 1 alpha administration to mice and tested IL 6 for radioprotection and induction of early (CSF) and late (fibrinogen and SAA) acute phase reactants. IL 1 alpha given to mice ip induced, in a dose dependent manner, detectable IL 6 in circulation, with maximal titers at 2-4 hrs. However, unlike IL 1 which is 10-1000 ng/mouse of human recombinant IL 6 did not result in increased survival of mice following lethal irradiation. In fact, such treatment given 20 hrs before LD50/30 doses of radiation resulted in reduced survival of mice. However, IL 6 augmented the radioprotective effect of IL 1. IL 1 in doses above 10 ng/mouse induced within 2 to 6 hrs a dose dependent increase in CSF in circulation, but IL 6 did not induce detectable levels of CSF at 2, 6 and 20 hrs after administration. Administration of IL 6 to mice produced a dose dependent increase in circulating fibrinogen and SAA. Similarly, administration of IL 1 resulted in much greater increases in levels of fibrinogen and SAA. Therefore, IL 1 is a more effective inducer of fibrinogen and SAA in mice than is IL 6. Although definitive conclusions concerning the relative roles for IL 1 and IL 6 in vivo will await availability of anti IL 1 and anti-IL 6 antibodies, our data do not support the suggestion that the above IL 1 effects can be attributed solely to IL 6.
Neta
R
R
Armed Forces Radiobiology Research Institute, Bethesda, MD 20814.
Vogel
S N
SN
Sipe
J D
JD
Wong
G G
GG
Nordan
R P
RP
D000210:Acute-Phase Reaction / Q000209:etiology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D004347:Drug Interactions; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D011837:Radiation-Protective Agents; D000685:Serum Amyloid A Protein / Q000096:biosynthesis
D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D011837:Radiation-Protective Agents; D000685:Serum Amyloid A Protein; D005340:Fibrinogen