Gene Expression of Hematoregulatory Cytokines is Elevated Endogenously After Sublethal Gamma Irradiation and is Differentially Enhanced by Therapeutic Administration of Biologic Response Modifiers
Abstract
Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicorynomycolate (S-TDCM) presumably accelerate hematopoietic recovery after irradiation by enhancing expression of cytokine. However, the kinetics of the cytokine gene response to BRMs and/or irradiation are poorly defined. One hour after sublethal (7.0 Gy) Cobalt gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrate marked splenic gene expression for IL-1 Beta, IL-6, and granulocyte-CSF(G CSF). Enhanced gene expression for TNF-Alpha, Macrophage-CSF (M CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater expression for IL-1 Beta, IL-3, TNF-alpha, and G-CSF at day 1 than any other BRM. When challenged with 2 LD50/30 of Klesiella pneumoniae 4 days after irradiation, 100% of SM-BRm-treated mice and 70% of S-TDCM-treated mice survived, whereas less than 30% of mice treated with LPS, MPL, or TS survived.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1994
- Accession Number
- ADA285821
Entities
People
- Gary S. Madonna
- Jeffrey J. Adamovicz
- Mary M. Moore
- Thomas B. Elliott
- Verlyn M. Peterson
Organizations
- Armed Forces Radiobiology Research Institute