Absence of interleukin 1 alpha radioprotection in tumor-bearing animals: elevated plasma levels of prostaglandin E versus a preexisting primed marrow.
Recombinant human interleukin 1 (IL-1) administered as a "priming" agent 24 h prior to hematopoietically lethal doses of total body irradiation (TBI) confers radioprotection to normal C57B1/6 (B6) mice, but not to B6 tumor-bearing animals (TBAs) known to have altered hematopoietic steady states. Using the Lewis lung tumor (LLca) in the B6 mouse, studies were carried out to determine whether the failure of IL-1 to radioprotect the LLca TBA was related to a preexisting "primed" hematopoietic state in the TBA or resulted from inhibition of myelopoietic activity associated with the production of prostaglandin E (PGE) by, or in response to, the tumor. Both normal B6 and LLca B6 TBAs were injected (every 24 h x 1-5) with 100 micrograms of indomethacin (IND) prior to the administration of IL-1. A single treatment with IND was sufficient to reduce the elevated levels of PGE found in the plasma of the TBAs. After five treatments, IND reduced the PGE level to below that of controls. Neither the acute nor the protracted IND treatment, however, affected the expansion of the stem and progenitor cell compartments of the marrow in the LLca TBA. Furthermore, no evidence of restoration of the radioprotective properties of IL-1 was observed in TBAs pretreated with IND. Collectively, these data suggest that the failure of IL-1 to provide radioprotection to the LLca TBA is not a direct result of the elevated plasma PGE levels associated with growth of the LLca tumor. In addition, these studies provide insight into the importance of examining in vivo effects of biological molecules in altered, as well as normal, physiological states.
Kovacs
C J
CJ
Department of Radiation Oncology, East Carolina University School of Medicine, Greenville, NC 27858.
Harrell
J P
JP
Evans
M J
MJ
Johnke
R M
RM
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D007375:Interleukin-1 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011458:Prostaglandins E / Q000097:blood*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014916:Whole-Body Irradiation
D007375:Interleukin-1; D011458:Prostaglandins E; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D007213:Indomethacin