Anti-IL-6 antibodies suppress myeloid cell production and the generation of CFU-c in long-term bone marrow cultures.
Interleukin 6 (IL-6) is one of several hemopoietic growth factors produced by stromal cell lines derived from the adherent layer of long-term bone marrow cultures (LTBMCs). To evaluate the potential role of IL-6 in stromal cell-dependent myelopoiesis, we established LTBMCs and verified that IL-6 mRNA is transcribed by heterogeneous adherent cell layers and that IL-6 protein is present in culture supernatants. Established LTBMCs were then depleted of IL-6 by using a specific neutralizing monoclonal antibody (mAb). Cultures treated for 2-3 weeks with anti-IL-6 mAb showed decreased production of maturing myeloid cells and colony-forming progenitor cells (colony-forming units in culture, CFU-c) but not stem cells (spleen colony-forming units, CFU-s). In parallel experiments, it was also found that the addition of IL-6 to LTBMCs stimulated a marked increase in total cell production, CFU-c, and day-8 CFU-s. In sum, it appears that endogenous production of IL-6, although limiting, is essential for the normal level of myelopoiesis associated with stromal cell function in LTBMCs.
Hudak
S
S
Department of Immunology, DNAX Research Institute, Palo Alto, California 94304.
Thompson-Snipes
L
L
Rocco
C
C
Jackson
J
J
Pearce
M
M
Rennick
D
D
D000818:Animals; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000235:genetics
D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D015850:Interleukin-6; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor