A phase I trial of recombinant human interleukin-1β alone and in combination with myelosuppressive doses of 5-fluorouracil in patients with gastrointestinal cancer

We studied escalating doses of recombinant human interleukin-1β (IL-1β) alone and after a myelosuppressive dose of 5-fluorouracil (5-FU) in patients with gastrointestinal cancer. Transient neutropenia, monocytopenia, and lymphocytopenia were observed followed by a 1.3- to 6.0-fold (mean, 3.46-fold) dose-dependent neutrophil leukocytosis (P < .00001 ) on the days of IL-1β administration. Increases in platelet counts were observed at a median of 14 days (range, 6 to 23) after IL-1β administration. Transient hypoglycemia, rebound hyperglycemia, elevations in serum cortisol, and C-reactive protein were observed. Side effects included fever, rigors, and headache in the majority of patients. Hypotension was observed in three of five patients at the highest dose level (0.1 μg/kg) and was dose-limiting. Fewer days of neutropenia were noted after 5-FU plus IL-1β than after 5-FU alone; however, this difference did not reach statistical significance. These data show that IL-1β has stimulatory effects in human hematopoiesis.