Aiming to study the dose-dependent effect of WIN 55,212-2 and anandamide (0,1; 1,0; 3,0 and 10,0 mcM) in vitro, blood probes were taken from 12 volunteers, whose level of proinflammatory mediators: cytokines (tumor necrosis factor (TNF-α), interleukin 8 (IL-8)) and eicosanoids (leukotriene B4 (LТВ4), thromboxane B2 (ТХВ2)) did not exceed norms. Blood cells were stimulated by lipopolysaccaride (LPS) Escherichia coli in dose 10 mg/ml. Basal and LPS-stimulated cytokine and eicosanoid production in whole blood was measured by means of the immunoenzymometric assay.

It was shown, that a spontaneous level of proinflammatory mediators in the blood probes, obtained from the donors, did not exceed the following values: TNF-α - 80 pg/ml, IL-8 - 115 pg/ml, LТВ4 - 110 pg/ml and ТХВ2 - 210 pg/ml. After the LPS-stimulation of the blood cells, the expression of mediators TNF-α increased 20-fold, IL-8 eight-fold, LТВ4 12-fold and ТХВ2 two-fold. The experiment showed, that low concentrations of WIN 55,212-2 and anandamide did not change the mediator production by LPS-stimulated blood cells. In concentration of 3,0 mcM, anandamide and WIN 55,212-2 reduced the synthesis of TNF-α, IL-8 and LТВ4. The strongest inhibiting effect on blood cells was achieved at concentration of 10,0 mcM. There were revealed no influence of the studied substances in different doses on ТХВ2 synthesis.

To sum up, the research on the dose-dependent effect of cannabinoid substances on proinflammatory mediator expression by blood cells showed, that cannabinoid-receptor ligands WIN55,212-2 and anandamide have a unidirectional anti-inflammatory effect on TNF-α, IL-8 and LТВ4 synthesis in human whole blood. The obtained data on the inhibiting effect of synthetic cannabinoids WIN55,212-2 and anandamide on proinflammatory mediator production could be used to develop new approaches to anti-inflammatory treatment.