Correlation between interleukin-1 production and engraftment of transplanted bone marrow stem cells in patients with lethal immunodeficiencies.
Interleukin-1 (IL-1) production by endotoxin-stimulated, cultured monocytes from 19 patients with lethal congenital immune disorders were studied and compared with normal controls. Lipopolysaccharide (LPS) stimulated IL-1 production was normal in three of three patients with Wiskott Aldrich syndrome (WAS), two of three combined immunodeficiency with T-cell predominance (CIDTP) and nine of 13 with severe combined immunodeficiency (SCID). Monocytes deficient in IL-1 production could be restored to normal production after incubation with indomethacin in three of five deficient patients. Monocytes from the other two patients could not be induced to generate IL-1, suggesting either an intrinsic deficiency or an alternate inhibitory mechanism as the basis for the IL-1 deficiency observed. In patients with SCID who were transplanted with HLA-haplotype disparate, T-cell depleted marrow without preparative chemotherapy, deficiency of monocyte IL-1 production was correlated with graft failure. Immune reconstitution was achieved in IL-1 deficient patients only when donor monocytes were also engrafted. We hypothesize that deficiencies of IL-1 production may contribute to the heterogeneous expression of combined immunodeficiencies, and may also restrict the engraftment and functional development of allogeneic lymphoid progenitors from a T-cell depleted marrow graft.
Sahdev
I
I
Department of Pediatrics, North Shore University Hospital, Cornell University Medical College, New York, NY 11030.
O'Reilly
R
R
Hoffman
M K
MK
D016026:Bone Marrow Transplantation; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology / Q000628:therapy*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D007375:Interleukin-1; D007213:Indomethacin