, Volume 25, Issue 5, pp 331-337

First online:

Influence of Low Molecular Weight Heparin (Certoparin) and Unfractionated Heparin on the Release of Cytokines from Human Leukocytes

  • M. KöllerAffiliated withDepartment of Surgery, BG Kliniken Bergmannsheil
  • , F. Kutscha-LissbergAffiliated withDepartment of Surgery, BG Kliniken Bergmannsheil
  • , J. BromAffiliated withNovartis Pharma
  • , G. WeidingerAffiliated withNovartis Pharma
  • , G. MuhrAffiliated withDepartment of Surgery, BG Kliniken Bergmannsheil

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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 × 106 cells/ml supplemented RPMI 1640. Leukocyte fractions were differentially stimulated (PMN with 1 μg and 5 μg LPS, PBMC with 10 ng TSST-1 or 2 μg ConA) in the presence or absence of heparins (1 U/ml, 2 U/ml, and 4 U/ml) for 24 h at 37°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.

Heparin cytokine leukocytes neutrophils