Low molecular weight heparin is associated with greater cytokine production in a stimulated whole blood model

Abstract

Anticoagulants can influence production of cytokines in whole blood, but the effects vary depending on the type of anticoagulant and the immunological stimulus. We examined this further by anticoagulating normal blood with either unfractionated (UF) heparin or low molecular weight heparin (Fragmin) and stimulating each sample with lipopolysaccharide, zymosan A, phytohemagglutinin, immune complexes, H2O2, or RPMI. After incubating 24 h, the combination of lipopolysaccharide and Fragmin induced significantly greater concentrations of interleukin 1 (IL)-1beta (25+/-10 ng/mL; x +/- standard error), IL-8 (21+/-6), and tumor necrosis factor (TNF)alpha (.48+/-.24) compared with heparinized blood (p < .05). The combination of Fragmin and zymosan also induced significantly greater concentrations of IL-1beta (97+/-24) and TNFalpha (2.9+/-.8), but not IL-8 (2.0+/-15). Average levels of proinflammatory cytokines (IL-1beta, IL-6, IL-8, and TNFalpha) were greater with Fragmin anticoagulation for 36 of 40 comparisons, and patterns were similar for 6 h and 24 h incubations. Statistical difference was established in 33% of these comparisons. A composite score of proinflammatory cytokines for Fragmin-anticoagulated blood was significantly greater than expected for UF heparinized blood (p < .0001) after 24 h. Expression of one anti-inflammatory cytokine (IL-10) was only slightly elevated for Fragmin anticoagulation. Proinflammatory cytokines are produced in greater quantities with Fragmin anticoagulation, which may be a disadvantage for ischemic conditions (e.g., cardiac surgery) but advantageous for long-term treatment of thrombosis.