Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1-, IL-17-, and G-CSF-dependent manner.
Neutropenia is a common side effect of cytotoxic chemotherapy and radiation, increasing the risk of infection in these patients. Here we examined the impact of body temperature on neutrophil recovery in the blood and bone marrow after total body irradiation (TBI). Mice were exposed to either 3 or 6 Gy TBI followed by a mild heat treatment that temporarily raised core body temperature to approximately 39.5°C. Neutrophil recovery was then compared with control mice that received either TBI alone heat treatment alone. Mice that received both TBI and heat treatment exhibited a significant increase in the rate of neutrophil recovery in the blood and an increase in the number of marrow hematopoietic stem cells and neutrophil progenitors compared with that seen in mice that received either TBI or heat alone. The combination treatment also increased G-CSF concentrations in the serum, bone marrow, and intestinal tissue and IL-17, IL-1β, and IL-1α concentrations in the intestinal tissue after TBI. Neutralizing G-CSF or inhibiting IL-17 or IL-1 signaling significantly blocked the thermally mediated increase in neutrophil numbers. These findings suggest that a physiologically relevant increase in body temperature can accelerate recovery from neutropenia after TBI through a G-CSF-, IL-17-, and IL-1-dependent mechanism.
Departments of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Maegan L
ML
Capitano
Michael J
MJ
Nemeth
Thomas A
TA
Mace
Christi
C
Salisbury-Ruf
Brahm H
BH
Segal
Philip L
PL
McCarthy
Elizabeth A
EA
Repasky
D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006410:Hematopoiesis / Q000502:physiology / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000528:radiation effects; D006358:Hot Temperature / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D020381:Interleukin-17; D016179:Granulocyte Colony-Stimulating Factor