In vivo restoration of T cell functions by human IL-1 beta or its 163-171 nonapeptide in immunodepressed mice.
The immunorestorative capacities of human (hu) IL-1 beta or its synthetic fragment 163-171 (VQGEESNDK) were assessed in vivo in mice immunodepressed by aging, sublethal irradiation, or both. Subcutaneous administration of hu rIL-1 beta into immunodepressed animals immediately after carrier (horse red blood cells, HRBC) priming could restore to normal levels Th cell activity. This was measured as the ability of spleen cells from HRBC-primed mice to induce a hapten-specific antibody response in spleen cells from nonimmune mice in vitro stimulated with the hapten-carrier conjugate TNP-HRBC. In parallel, the ability of spleen cells from hu rIL-1 beta-treated immunodepressed animals to produce T cell growth factor activity upon in vitro mitogen stimulation was also increased significantly as compared to that of untreated mice and approached that of immunocompetent controls. The immunorestorative activity of hu rIL-1 beta on Th cell activity and T cell growth factor production could be mimicked by the synthetic nonapeptide 163-171 which, at the doses used, produced in most instances even greater effects than the whole protein. Although the optimal immunorestorative doses of the 163-171 peptide were several orders of magnitude higher than those of hu rIL-1 beta, the complete lack of IL-1-like inflammatory and toxic effects suggests that the synthetic hu IL-1 beta fragment may be successfully used as immunomodulating agent in the therapy of T cell immunodeficiencies.
Frasca
D
D
Laboratory of Pathology, ENEA C.R.E. Casaccia, Roma, Italy.
Boraschi
D
D
Baschieri
S
S
Bossu
P
P
Tagliabue
A
A
Adorini
L
L
Doria
G
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000375:Aging / Q000528:radiation effects; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D007375:Interleukin-1 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000528:radiation effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D014916:Whole-Body Irradiation
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D007376:Interleukin-2; D010446:Peptide Fragments; D011994:Recombinant Proteins