Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models.
Human rIL-1 alpha and -1 beta are shown to increase significantly the CFU-culture activity in the spleen as well as at other sites after i.v. or i.p. administration. IL-1 can also significantly increase survival and can "rescue" a number of animals if administered either before or after lethal doses of cyclophosphamide or gamma-irradiation. The protective and reconstitutive activities of the rIL-1 are shown to correlate with increased CFU-culture frequency and total number, as well as increased cellularity in the bone marrow and peripheral blood, suggesting that this is one of their mechanisms of action. The sequence and timing of administration of human rIL-1 is critical for the protection or rescue of animals receiving DNA-damaging agents; maximal activity is achieved when IL-1 is given 20 h before insult or 48 h after alkylating agent administration. Minimal therapeutic activity is observed with IL-1 as a single agent for the treatment of metastatic disease compared with other biologic response modifiers including IFN-gamma.
Castelli
M P
MP
Preclinical Screening Laboratory, National Cancer Institute-Frederick Cancer Research Facility, MD 21701.
Black
P L
PL
Schneider
M
M
Pennington
R
R
Abe
F
F
Talmadge
J E
JE
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000633:toxicity; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000627:therapeutic use*; D007700:Kinetics; D007928:Lethal Dose 50; D007970:Leukopenia / Q000139:chemically induced / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011833:Radiation Injuries, Experimental / Q000401:mortality / Q000517:prevention & control; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*
D007375:Interleukin-1; D011994:Recombinant Proteins; D003520:Cyclophosphamide