Interleukin 6 perfusion stimulates reconstitution of the immune and hematopoietic systems after 5-fluorouracil treatment.
Effects of interleukin 6 (IL-6) on the functional capacity of the immune and hematopoietic systems in 5-fluorouracil (5-FU)-treated mice were determined. IL-6 (5 x 10(4) units/mouse/day) was administered s.c. for 7 days by implantation of an osmotic pump, since it was demonstrated that a much higher increase in the primary response to sheep RBC was observed by administration of slowly released rather than daily s.c. injection of IL-6. IL-6 perfusion significantly augmented anti-sheep RBC antibody responses depressed by 5-FU (150 mg/kg) treatment. IL-6 also was shown to stimulate hematological recovery in mice treated with 5-FU. Namely, IL-6 perfusion accelerated the recovery of the number of hematopoietic stem cells, granulocyte-macrophage progenitors, and mature neutrophils in the spleen, although IL-6 did not stimulate the recovery of the neutrophil count in blood. Recovery of the platelet count in blood was stimulated by IL-6. Furthermore, it was found that the endogenous IL-6 level in serum increased after 5-FU treatment, which suggests that IL-6 may play some role in the recovery of the immune and hematopoietic systems. Finally, we examined the effect of IL-6 on the survival of mice treated with a higher dosage of 5-FU (300 mg/kg). IL-6 perfusion produced a distinct increase in survival rate at Day 30 (74% versus 28%). It is of note that the number of bacteria (identified as Escherichia coli) cultured from the spleen and the liver decreased in IL-6-perfused mice. This IL-6-induced effect was accompanied by enhancement of an oxidative burst response. Moreover, the anti-E. coli antibody titer in serum was higher in IL-6-perfused mice than in control mice. These results suggest the possible use of IL-6 for stimulating the reconstitution of the immune and hematopoietic systems after chemotherapy treatment.
Takatsuki
F
F
Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Okano
A
A
Suzuki
C
C
Miyasaka
Y
Y
Hirano
T
T
Kishimoto
T
T
Ejima
D
D
Akiyama
Y
Y
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001772:Blood Cell Count / Q000187:drug effects; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D007109:Immunity / Q000187:drug effects*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors
D015850:Interleukin-6; D005472:Fluorouracil