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Developmental Regulation of the Cytokine Repertoire in Human Macrophages: IL‐1, IL‐6, TNF‐α, and M‐CSF
Author(s) -
Scheibenbogen Carmen,
Andreesen Reinhard
Publication year - 1991
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.50.1.35
Subject(s) - cytokine , tumor necrosis factor alpha , biology , lipopolysaccharide , secretion , endocrinology , macrophage , immunology , medicine , interleukin , interleukin 6 , in vitro , biochemistry
We were interested in the dependence of constitutive and stimulated cytokine secretion on the stage of macrophage (MAC) differentiation in vitro. Elutriation‐purified blood MO were cultured up to 28 days and their secretory repertoire was analyzed under adherence conditions at various culture stages. For each of the cytokines tested, interleukin (IL)‐1β, IL‐6, tumor necrosis factor (TNF)‐α, and macrophage colony‐stimulating factor (M‐CSF), a different pattern of regulation was observed. During the initial phase of maturation (up to day 7 in culture) within which the characteristics of normal MO to MAC transformation are achieved, M‐CSF was the only cytokine to be secreted constitutively. From the LPS‐dependent cytokines, IL‐1β and IL‐6 were downregulated whereas TNF‐α levels increased severalfold. For the release of IL‐1β, IL‐6, and TNF‐α a synergistic effect of interferon‐gamma (IFN‐g) and lipopolysaccharide (LPS) was observed. M‐CSF release increased until day 7 in culture with LPS being stimulatory for this particular cytokine only during the first days of differentiation. Upon further cultivation of MAC up to 28 days, LPS‐induced IL‐1β levels remained very low, but IL‐6 levels increased again reaching that of blood MO, and TNF‐α continued to rise reaching levels up to 30‐fold higher than in blood MO. M‐CSF secretion stayed high with LPS even suppressing constitutive secretion. Long‐term cultured MAC started to release IL‐6 and TNF‐α also in the absence of a stimulus and, furthermore, became responsive to IFN‐g alone. Our data show that the release of each cytokine investigated is differently regulated during maturation. These results document the functional plasticity of human MAC and emphasize the impact that MO to MAC differentiation may have in vivo.