Interleukin-6 ablates the accessory cell-mediated suppressive effects of lactoferrin on human hematopoietic progenitor cell proliferation in vitro.
LF, an iron-binding glycoprotein, has myelosuppressive effects in vitro and in vivo. The present study evaluated the mode of LF action in vitro and the effects of various recombinant CSFs and ILs on this action. Normal human low-density BMC, at 2 x 10(6)/ml, were exposed to purified and endotoxin-depleted iron-saturated LF for 2 h, washed three times, and plated for CFU-GM and BFU-E in the presence of rhuCSFs (e.g., GM-CSF, Epo, IL-3) and in the absence and presence of rhuIL-6, rhuIL-1 alpha, or rhuIL-1 beta. LF caused a 40-65% plateau curve of inhibition for CFU-GM and BFU-E that was not apparent when adherent mononuclear cells (monocytes) were removed from the target population of cells. This myelosuppression was ablated by rhuIL-6, but not by rhuIL-1 alpha or rhuIL-beta. These results suggests a role for IL-6 in the accessory cell-mediated suppressive effect of LF on CFU-GM and BFU-E and open up the possibility that IL-6 may have stimulatory/enhancing or cofactor activities necessary for optimal proliferation of hematopoietic progenitor cells.
Gentile
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Department of Medicine Hematology/Oncology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202-5121.
Broxmeyer
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HE
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D007781:Lactoferrin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D007781:Lactoferrin