Influence of Low Molecular Weight Heparin (Certoparin) and Unfractionated Heparin on the Release of Cytokines from Human Leukocytes
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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.
- Fareed, J., D. A. Hoppensteadt, and R. L. Bick. 2000. An update on heparins at the beginning of the new millennium. Semin. Thromb. Hemost. 26(Suppl 1):5–21
- Weitz, J. I. 1997. Low-molecular-weight heparins. New Engl. J. Med. 337:688–698.
- Lever, R., J. R. Hoult, and C. P. Page. 2000. The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leucocytes to vascular endothelium in vitro. Br. J. Pharmacol. 129: 533–540.
- Donata, P., T. Qutob, W. Hamouda, F. Bakri, A. Aljada, and Y. Kumbkarni. 1999. Heparin inhibits reactive oxygen species generation by polymorphonuclear and mononuclear leucocytes. Thromb. Res. 96:437–443.
- Nelson, R. M., O. Cecconi, W. G. Roberts, A. Aruffo, R. J. Linhardt, and M. P. Bevilacqua. 1993. Heparin oligosaccharides bind L-and P-selectin and inhibit acute inflammation. Blood 82:3253–3258.
- McBride, W. T., M. A. Armstrong, and T. J. McMurray. 1996. An investigation of the effects of heparin, low molecular weight heparin, protamine, and fentanyl on the balance of pro-and antiinflammatory cytokines in in-vitro monocyte cultures. Anaesthesia 51:634–640.
- Heinzelmann, M., M. Miller, A. Platz, L. E. Gordon, D. O. Herzig, H. C. Polk Jr. 1999. Heparin and enoxaparin enhance endotoxininduced tumor necrosis factor-alpha production in human monocytes. Ann. Surg. 229:542–550.
- Call D. R., and D. G. Remick. 1998. Low molecular weight heparin is associated with greater cytokine production in a stimulated whole blood model. Shock 10:192–197.
- Baram, D., M. Rashkovsky, R. Hershkoviz, I. Drucker, T. Reshef, S. Ben-Shitrit, and Y. A. Mekori. 1997. Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation. Clin. Exp. Immunol. 110:485–491.
- Engstad, C. S., T. J. Gutteberg, and B. Osterud. 1997. Modulation of blood cell activation by four commonly used anticoagulants. Thromb. Haemost. 77:690–696.
- English, D., and B. R. Andersen. 1974. Single step separation of red blood cells, granulocytes and mononuclear leukocytes on discontinuous density gradient of ficoll-hypaque. J. Immunol. Methods 5:249–252.
- Köller, M., P. Wachtler, A David, G. Muhr, and W. König. 1997. Arachidonic acid induces DNA-fragmentation in human polymorphonuclear neutrophil granulocytes. Inflammation 21:463–474.
- Altstaedt, J., H. Kirchner, and L. Rink. 1996. Cytokine production of neutrophils is limited to interleukin-8. Immunology 89:563–568.
- Sweeney, J. F., P. K. Nguyen, G. M. Omann, and D. B. Hinshaw. 1997. Ultraviolet irradiation accelerates apoptosis in human polymorphonuclear leukocytes: protection by LPS and GM-CSF. J. Leuko. Biol. 62:517–523.
- Esmon, C. T., K. Fukudome, T. Mather, W. Bode, L. M. Regan, D. J. Stearns-Kurosawa, and S. Kurosawa. 1999. Inflammation, sepsis, and coagulation. Haematologica 84:254–259.
- Hoffman, M., and S. T. Cooper. 1995. Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms. Blood Cells Mol. Dis. 21:156–167.
- Dinarello, C. A. 1998. Interleukin-1. In: The Cytokine Handbook. Ed. A. Thomson. Academic Press, San Diego, pp. 35–72.
- Tilg, H., C. A. Dinarello, and J. W. Mier. 1997. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol. Today 9:428–432.
- De Waal Malefyt, R., H. Yssel, M. G. Roncarolo, H. Spits, and J. E. De Vries. 1992. Interleukin-10. Curr. Opinion Immunol. 4:314–320.
- Storkus, W. J., H. Tahara, and M. T Lotze. 1998. Interleukin-12. In: The Cytokine Handbook. Ed. A. Thomson. Academic Press, San Diego, pp. 391–426.
- Darien, B. J., J. Fareed, K. S. Centgraf, A. P. Hart, P. S. MacWilliams, M. K. Clayton, H. Wolf, and K. T. Kruse-Elliott. 1998. Low molecular weight heparin prevents the pulmonary hemodynamic and pathomorphologic effects of endotoxin in a porcine acute lung injury model. Shock 9:274–281.
- Schwartz, D., D. Engelhard, R. Gallily, I. Matoth, and T. Brenner. 1998. Glial cells production of inflammatory mediators induced by Streptococcuspneumoniae: inhibition by pentoxifylline, lowmolecular-weight heparin and dexamethasone. J. Neurol. Sci. 18:13–22.
- Mummery, R. S., and C. C. Rider. 2000. Characterization of the heparin-binding properties of IL-6. J. Immunol. 165:5671–5679.
- Balasubramanian, V., and M. Ramanathan. 2000. Glycosaminoglycans alter the conformation of interferon-gamma. Cytokine 12:466–471.
- Influence of Low Molecular Weight Heparin (Certoparin) and Unfractionated Heparin on the Release of Cytokines from Human Leukocytes
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