THE EFFECT OF JOINT INFLUENCE OF THE COMBINED EFFECT OF METHOTREXATE WITH PHYTOEXTRACTS OF MEDOW CLOVER AND COMMON CHICORY ON THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES IN VITRO

Abstract

Introduction. One of the aspects of limiting the toxicity of methotrexate (MTX) is the use of herbal remedies, which are characterized by such properties as availability, safety and high biological activity in combination with very low toxicity. Among the medicinal plants containing a large complex of biologically active substances of a polyphenolic nature and possessing antioxidant, anti-inflammatory, immunocorrective and other properties, meadow clover and common chicory should be singled out. Phytoextracts obtained from these plants can be used to protect against the immunosuppressive effect of methotrexate and enhance its anti-inflammatory properties without inducing MTX toxicity. At the same time, it should be noted that information on the mechanisms of anti-inflammatory activity of individual phytoextracts is multidirectional.

The aim of the work: to evaluate the effect of clover and chicory phytoextracts on the secretion of proinflammatory cytokines TNFα, IL-6 and IL-17 by human peripheral blood mononuclear cells under methotrexate-induced immunosuppression.

Materials and methods. Dry extracts from clover grass and chicory grass were obtained by percolation with ethyl alcohol. The production of cytokines TNFα, IL-6 and IL-17 in the supernatants of unstimulated and concanavalin A (Con A) stimulated human peripheral blood mononuclear cell cultures was assessed using the enzyme immunoassay method.

Results. Evaluation of the immunoregulatory activity of dry extracts from clover and chicory grass, as well as their combinations with methotrexate on the model of human peripheral blood mononuclear cells showed that the phytoextracts suppressed the production of proinflammatory cytokines in the in vitro system, both spontaneous (TNFα, IL-6) and induced (TNFα, IL-6 and IL-17). It should be noted that the severity of the inhibitory effect of phytoextracts was not inferior, and in relation to individual cytokines (TNFα and IL-17) was superior to the phytopreparation «Immunal».

Conclusions:

1. The inhibitory effect of clover and chicory phytoextracts, as well as their combinations with MTX on the production of proinflammatory cytokines by human peripheral blood mononuclear leukocytes - TNFα, IL-6, IL-17 was established.
2. The potentiating effect of phytoextracts on enhancing the inhibitory effect of the cytostatic MTX on the production of IL-6 by lymphocytes and the appearance of an anti-inflammatory effect on TNFα and IL-17 was shown.
3. The most pronounced immunoregulatory and potentiating effect on the anti-inflammatory effect of MTX was demonstrated by the chicory phytoextract, with both extracts exceeding the effect of the comparison drug «Immunal».