Promotion of murine marrow alloengraftment and hematopoietic recovery across the major histocompatibility barrier by administration of recombinant human interleukin-1α

• Published in: Blood 1992-09, Vol.80 (6), p.1614-1622
• Main Authors: BLAZAR, B. R, WIDMER, M. B, TAYLOR, P. A, VALLERA, D. A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow Transplantation - immunology; Female; Graft Survival - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Immunomodulators; Injections, Subcutaneous; Interleukin-1 - pharmacology; Major Histocompatibility Complex - physiology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pharmacology. Drug treatments; Recombinant Proteins - pharmacology; Spleen - cytology; Time Factors; Transplantation, Homologous - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V80.6.1614.1614

Irradiated C57BL/6 (H-2b) recipients of T-cell-depleted (TCD) BALB/c (H-2d) bone marrow (BM) and recombinant interleukin-1 alpha (IL-1 alpha) (1 microgram/d) had a significantly (P less than or equal to .006) higher 100-day actuarial survival rate, accelerated hematopoietic recovery, and higher levels of alloengraftment than a group of transplanted control mice treated identically, but given phosphate-buffered saline (PBS). To elucidate the mechanisms involved with IL-1 alpha-induced promotion of alloengraftment and hematopoietic recovery, we performed sequential splenic FACS studies on transplanted mice and secondary transfer studies in syngeneic mice given IL-1 alpha or PBS. Splenic phenotyping showed that recipients of IL-1 alpha had a higher proportion of donor granulocytes (52% v 19%) as compared with PBS controls as early as 7 days after bone marrow transplantation (BMT). On day 11 post-BMT, recipients of IL-1 alpha had a more than fourfold increase in splenocyte number, which included a higher percentage (90% v 59%) of donor cells, especially donor granulocytes (52% vs 32%), and a sevenfold increase in donor T cells as compared with controls. Host T-cell numbers were not affected. Taken together, these data suggest that IL-1 alpha stimulated bipotential (myeloid and lymphoid) donor cell engraftment. In a syngeneic BMT system, administration of IL-1 alpha resulted in a higher incidence of survival when recipients were transplanted with BM cells, indicating that IL-1 alpha administration probably either expanded or potentiated engraftment of a committed progenitor cell pool. Secondary transfer experiments using marrow from IL-1 alpha-treated mice showed that the number of day 12 colony-forming unit-spleen (CFU-S) cells was unaltered compared with untreated control mice, suggesting that more primitive, albeit committed, hematopoietic progenitor cells were not affected. We also examined the potential additive effects of IL-1 alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) administered in combination (for 14 days). Mice receiving a suboptimal amount of IL-1 alpha along with GM-CSF had significantly higher levels of donor alloengraftment (92%) with superior hematopoietic recovery, as compared with mice receiving either IL-1 alpha (57%) or GM-CSF (18%) alone.