Interleukin-1: biological effects in human hematopoiesis.
Interleukin-1 (IL-1) produces many direct and indirect effects in hematopoiesis. Il-1 stimulates hematopoietic progenitors, and enhances production of other cytokines. Experimental data suggest a role in ameliorating the myelosuppression that occurs following cytotoxic chemotherapy. Recombinant human interleukin-1 has now entered clinical trial. We conducted a phase I trial of IL-1 beta alone, and following a myelosuppressive dose of 5-fluorouracil in patients with cancer. A prominent neutrophilia was noted within several hours, with a later, more sustained thrombocytosis. Hypotension was dose-limiting. We observed fewer days of neutropenia following 5-FU plus IL-1 compared to IL-1 alone, but the difference did not reach statistical significance. Early results from other investigators suggest a possible protective effect from chemotherapy-induced myelosuppression. Preclinical data suggest that combinations of IL-1 and lineage specific growth factors may produce synergistic hematologic effects.
Crown
J
J
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Jakubowski
A
A
Gabrilove
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000097:blood; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016207:Cytokines; D007375:Interleukin-1; D011994:Recombinant Proteins