In vivo stimulation and restoration of the immune response by the noninflammatory fragment 163-171 of human interleukin 1 beta.
The synthetic nonapeptide VQGEESNDK, corresponding to the fragment 163-171 of human IL-1 beta, showed in vivo immunomodulatory capacities qualitatively and quantitatively comparable to those of the mature human IL-1 beta protein. In fact, both IL-1 beta and the 163-171 fragment stimulated the immune response of normal mice and restored immune reactivities of immunocompromised animals. In addition, the synthetic IL-1 peptide was as efficient as the entire protein in inducing tumor rejection and radioprotection. On the other hand, the 163-171 fragment did not cause any of several inflammation-associated metabolic changes inducible by the whole IL-1 beta molecule in vivo: hypoferremia, hypoglycemia, hyperinsulinemia, increase in circulating corticosterone, SAA and fibrinogen, decrease in hepatic drug-metabolizing enzymes. Furthermore, at variance with IL-1 beta, the 163-171 peptide did not show the toxic effects causing shock and death in adrenalectomized mice. Thus, these results confirm our previous in vitro observations that functional domains are identifiable within the multipotent cytokine IL-1 beta, and demonstrate the biological relevance of this finding in a variety of in vivo systems. The identification of a selectively active fragment of a cytokine may thus represent a significant step towards a better directed and more rational immunotherapeutic approach.
Boraschi
D
D
Sclavo Research Center, Siena, Italy.
Nencioni
L
L
Villa
L
L
Censini
S
S
Bossù
P
P
Ghiara
P
P
Presentini
R
R
Perin
F
F
Frasca
D
D
Doria
G
G
D015660:7-Alkoxycoumarin O-Dealkylase; D000315:Adrenalectomy; D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006728:Hormones / Q000097:blood; D007114:Immunization; D007375:Interleukin-1 / Q000138:chemical synthesis / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology*; D010105:Oxygenases / Q000378:metabolism; D012769:Shock / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D006728:Hormones; D007375:Interleukin-1; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase