Radiation protection and restoration by the synthetic 163-171 nonapeptide of human interleukin 1 beta.
We have previously reported that the synthetic nonapeptide VQGEESNDK, position 163-171 of human interleukin 1 (IL-1 beta), when injected in immunodepressed mice, shows immunorestorative activity similar to that of the whole protein, but with no IL-1-like inflammatory effects [Frasca et al., J. Immunol. 141, 2651-2655 (1988)]. In the present study we have compared the protective and restorative activities of the nonapeptide and human recombinant (hur) IL-1 beta on the survival of lethally irradiated mice. When mice were given a single injection of different doses of the nonapeptide or hurIL-1 beta 20 h before total-body irradiation, both molecules increased the percentage survival of mice exposed to 750 or 850 cGy, but not to 950 cGy. The nonapeptide, however, is less effective than hurIL-1 beta and displays a different dose-response relationship, suggesting that the two molecules act through different radioprotective pathways. When mice were injected with the nonapeptide or hurIL-1 beta immediately after exposure to 850 cGy, the percentage survival was also increased but restoration was lower than protection in both cases. The nonapeptide was also less effective than hurIL-1 beta in restoration, but the two molecules displayed a comparable dose-response relationship as if they shared similar mechanisms. These findings indicate that the 163-171 nonapeptide is able to protect from lethal radiation injury and to restore viability. The nonapeptide appears less effective than hurIL-1 beta but does not exhibit the IL-1-like side effects of the whole molecule.
Frasca
D
D
Laboratory of Pathology, ENEA C.R.E. Casaccia, Rome, Italy.
Baschieri
S
S
Boraschi
D
D
Tagliabue
A
A
Doria
G
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000627:therapeutic use*; D053583:Interleukin-1beta; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; C052994:interleukin-1beta (163-171)