Effects of interleukin 3 and interleukin 6 on platelet recovery in mice treated with 5-fluorouracil.
We have studied the effects of murine recombinant interleukin 3 (IL-3) and human recombinant interleukin 6 (IL-6) on platelet recovery after administration of 5-fluorouracil (5-FU) to mice. 5-FU at 250 mg/kg body weight was administered as a single i.p. injection, and treatment with IL-3 alone, IL-6 alone, or a combination of IL-3 plus IL-6 was initiated immediately following the 5-FU or after a delay of 2 days. In addition, the effects of the combination of IL-3 plus IL-6 were evaluated following delays in initiation of their administration until 4 or 6 days after 5-FU treatment. In all schedules, the IL-3 and IL-6 treatments were discontinued 8 days following 5-FU. IL-3 and IL-6 were given s.c. three times daily; each injection of IL-3 was 80,000 U, each injection of IL-6 was 5000 U, and the combination comprised separate injections of IL-3 and IL-6 at the same respective doses. The combination of IL-3 and IL-6, initiated immediately or 2 days following 5-FU, diminished the platelet nadir and increased platelet counts on individual days during the recovery phase, thus apparently decreasing the time required for recovery to a normal platelet level. However, using self-modeling nonlinear regression, in order to analyze variability in the duration of thrombocytopenia, statistically significant shortening of the period of thrombocytopenia could not be consistently demonstrated. Neither IL-3 alone nor IL-6 alone had any effect on the above parameters. Recovery of hematocrit values and white blood cell levels was unaffected by administration of either IL-3 or IL-6 alone or the combination of both cytokines. We propose that IL-3 and IL-6 can act synergistically to enhance platelet recovery following 5-FU-mediated thrombocytopenia, but their modification of the response to 5-FU is modest.
Carrington
P A
PA
Department of Laboratory Medicine, University of California School of Medicine, San Francisco.
Hill
R J
RJ
Levin
J
J
Verotta
D
D
D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D007377:Interleukin-3 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000008:administration & dosage*; D051379:Mice; D010976:Platelet Count
D007377:Interleukin-3; D015850:Interleukin-6; D005472:Fluorouracil