title: Relative cytokine and cytokine inhibitor production by mononuclear cells and neutrophils.
abstract: Mononuclear cells represent the major source of cytokines in blood; however, it has been postulated that neutrophils may produce and/or release modest amounts of cytokines. In this study, we compared the production of cytokines and cytokine inhibitors in lipopolysaccharide (LPS)-stimulated whole blood, peripheral blood mononuclear cells (PBMCs), and neutrophils (PMNs) separated by density gradient centrifugation. Contamination of PBMCs in the isolated PMNs was less than 0.1% as determined by morphological analysis and flow cytometry. LPS (50 ng/mL) induced a strong increase of the proinflammatory cytokines tumor necrosis factor, interleukin (IL)-1beta, IL-8, and IL-6 in whole blood. In the isolated cell preparations, proinflammatory cytokine production was significantly greater in the PBMCs compared with the PMNs. On a per cell basis, PMNs produced less than 1.5% of these cytokines compared with PBMCs. For cytokine inhibitors, TNF-soluble receptor type II and IL-1 receptor antagonist were increased by LPS stimulation in whole blood, PBMCs, and PMNs. On a per cell basis, LPS-induced TNF-soluble receptor type II and IL-1 receptor antagonist production by PMNs was 9.8% and 15.4% of those of PBMCs, respectively. These data show that a highly purified population of PMNs makes a relatively minor to nonexistent contribution to the production of proinflammatory cytokines.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Medical Science Building 1, 1301 Catherine Road, Ann Arbor, MI 48105, USA.
authors.forename: Liyu
authors.initials: L
authors.lastname: Xing
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D015703:Antigens, CD / Q000378:metabolism* / Q000494:pharmacology; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins