title: Influence of low molecular weight heparin (certoparin) and unfractionated heparin on the release of cytokines from human leukocytes.
abstract: We analyzed the influence of heparins (unfractionated heparin, UFH and low molecular weight heparin certoparin) on the generation of IL-1ra, IL-6, IL-10, and IL-12p40 and from leukocyte fractions in vitro. Polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from 16 different healthy donors were isolated and adjusted to 1 x 10(6) cells/ml supplemented RPMI 1640. Leukocyte fractions were differentially stimulated (PMN with 1 microg and 5 microg LPS, PBMC with 10 ng TSST- 1 or 2 microg ConA) in the presence or absence of heparins (1 U/ml, 2 U/ml, and 4 U/ml) for 24 h at 37 degrees C. Cytokine release was analyzed by ELISA. Certoparin but not UFH led to a dose-dependent increase in IL-6 from non-stimulated PBMC. In contrast, the release of IL-1ra, IL-10, and IL-12p40 was not modulated by heparins in a dose-dependent fashion. Increases in these cytokines occurred only as single incidents at intermediate heparin levels. An influence of the heparins on the apoptosis of PMN (measured as DNA-fragmentation in non-stimulated or LPS-stimulated cell-fractions) was not observed.
authors.affiliation: Department of Surgery, BG Kliniken Bergmannsheil, Bochum, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Köller
authors.forename: F
authors.initials: F
authors.lastname: Kutscha-Lissberg
authors.forename: J
authors.initials: J
authors.lastname: Brom
authors.forename: G
authors.initials: G
authors.lastname: Weidinger
authors.forename: G
authors.initials: G
authors.lastname: Muhr
mesh_terms: D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism
chemical_list: D016207:Cytokines; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D018836:Inflammation Mediators; D006493:Heparin; C403769:certoparin