ИСТИНА

Anti‐cytokine therapy aimed at blocking pathogenic cytokines is promising in the treatment of disorders associated with chronic inflammation. TNF and IL‐6 are the key mediatorsof inflammation that play an important role in the pathogenesis of asthma. Notwithstanding, studies using anti‐IL‐6 or anti‐TNF therapeutic antibodies failed to provide positiveoutcomes for patients with poorly controlled asthma and the efficacy of combined inhibition of TNF and IL‐6 in asthma were not studied. The aim of the study was to investigatewhether the simultaneous administration of anti‐TNF/IL‐6 antibodies will be beneficial in the context of severe asthma. To address the efficacy of combined therapy we induced acuteasthma in BALB/c mice by daily intranasal administration of 20 μg HDM extract for a week with sensitization of 5 μg HDM one week prior to the main course. Anti‐IL‐6 antibodies(MP5‐20F3) and anti‐TNF inhibitor (Etanercept) were administered intraperitoneally prior to each immunization. We found that combined anti‐TNF/IL‐6 inhibition decreasedgranulocyte infiltrate, as well as the production of IgE in BALF as compared to inhibition of these cytokines individually. In addition, the simultaneous administration of the inhibitorsled to diminished expression of IL‐17A and to reduction of Th17 cell recruitment in the lungs induced by anti‐TNF monotherapy. Taken together, the data suggest that combinedpharmacological inhibition of TNF и IL‐6 in mixed granulocytic asthma may be more beneficial compared to inhibition of these cytokines individually.