Monocytes are the major producers of interleukin-1 beta in an ex vivo model of local cytokine production.
Interleukin-1 beta (IL-1 beta) is an early proinflammatory cytokine with multiple effects. Several cells are capable of synthesizing this cytokine, but little is understood about which cell produces IL-1 in disease states. We examined the cellular source of IL-1 in lipopolysaccharide (LPS)-stimulated human whole blood. Cytospin preparations of leukocytes were stained for IL-1 beta using a murine monoclonal antibody and staining intensity evaluated. In multiple time course experiments, LPS-stimulated whole blood showed increases in both plasma and cell-associated IL-1 beta over 8 h as measured by ELISA (at 4 h, plasma IL-1 beta, 7.2 +/- 2.7 ng/ml; cell lysates, 1.3 +/- 0.2 ng/ml). Northern blot confirmed the upregulation of IL-1 beta mRNA in leukocytes. Immunohistochemistry showed low-level PMN positivity with no increase in staining intensity over time. In contrast, monocytes displayed a marked increase in staining intensity by 4 h, correlating with increases in cell-associated and plasma IL-1 levels. Lymphocytes remained negative throughout. Our data demonstrate that monocytes represent the major source of IL-1 beta in a human ex vivo model that simulates physiologic conditions and stimuli.
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Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Remick
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D001483:Base Sequence; D015152:Blotting, Northern; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D013268:Stimulation, Chemical
D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides