Recombinant Interleukin-1 Alpha and Recombinant Tumor Necrosis Factor Alpha Synergize in Vivo to Induce Early Endotoxin Tolerance and Associated Hematopoietic Changes
Abstract
Endotoxin, the lipopolysaccharide (LPS) derived from gram-negative bacteria, invokes a wide range of responses in susceptible hosts. It is known that virtually all responses to LPS are mediated by the action of macrophage- derived cytokines (such as interleukin-1 IL-1, tumor necrosis factor TNF, and others) which are produced principally by macrophages and maximally within several hours of LPS administration. In this study, we examined the capacity of recombinant Il-1 or recombinant TNF or both to induce early endotoxin tolerance and its associated hematopoietic changes. Neither cytokine alone was able to mimic LPS for induction of tolerance. Combined administration of recombinant IL- 1 and recombinant TNF doses which were not toxic when administered individually led to synergistic toxicity (as assessed by death or weight loss). However, within a nontoxic range, the two cytokines synergized to induce a significant reduction in the capacity to produce colony-stimulating factor in response to LPS, as well as the characteristic increase in bone marrow cell size and macrophage progenitors shown previously to be associated with LPS-induced tolerance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1988
- Accession Number
- ADA202517
Entities
People
- Eric N. Kaufman
- Michele D. Tate
- Ruth Neta
- Stefanie N. Vogel
Organizations
- Armed Forces Radiobiology Research Institute