Interdependence of the radioprotective effects of human recombinant interleukin 1. cap alpha. , tumor-necrosis factor. cap alpha. , granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor

Technical Report · Fri Jan 01 04:00:00 EST 1988

OSTI ID:6895840

Neta, R; Oppenheim, J J; Douches, S D

Interleukin 1..cap alpha.. (lL-1..cap alpha..), tumor-necrosis factor ..cap alpha.. (TNF..cap alpha..), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) are molecularly distinct cytokines acting on separate receptors. The release of these cytokines can be concomitantly induced by the same signal and from the same cellular source, suggesting that they may cooperate. Administered alone, human recombinant (hr)IL-1..cap alpha.. and hrTNF..cap alpha.. protect lethally irradiated mice from death, whereas murine recombinant GM-CSF and hrG-CSF do not confer similar protection. On a dose basis, IL-1..cap alpha.. is a more efficient radioprotector than TNF..cap alpha... At optimal doses, IL-1..cap alpha.. is a more-radioprotective cytokine than TNF..cap alpha.. in C57BL/6 and B6D2F1 mice and less effective than TNF..cap alpha.. and C3H/HeN mice, suggesting that the relative effectiveness of TNF..cap alpha.. and IL-1..cap alpha.. depends on the genetic makeup of the host. Administration of the two cytokines in combination results in additive radioprotection in all three strains. This suggests that the two cytokines act through different radioprotective pathways and argues against their apparent redundancy. Suboptimal, nonradioprotective doses of IL-1..cap alpha.. also synergize with GM-CSF or G-CSF to confer optimal radioprotection, suggesting that such an interaction may be necessary for radioprotection of hemopoietic progenitor cells.

• Research Organization: Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)
• OSTI ID: 6895840
• Report Number(s): AD-A-192770/6/XAB; AFRRI-SR-87-43
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDITIVES
ANIMALS
BIOCHEMISTRY
CHEMISTRY
CYTOCHEMISTRY
DEATH
DISEASES
DRUGS
EFFICIENCY
IRRADIATION
LETHAL IRRADIATION
MAMMALS
MICE
NECROSIS
NEOPLASMS
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PEPTIDES
PROTEINS
RADIATION PROTECTION
RADIOPROTECTIVE SUBSTANCES
RODENTS
VERTEBRATES