Character of intersystem interactions in patients with asthma

Introduction. Disruption of the interactions among parameters of oxidative homeostasis, cell signalling and cellular energetic status leads to failure of adaptive mechanisms, which favours progression of pathological changes in asthma. Aim. To determine the character of intersystem interactions in mild and moderate controlled and partially controlled asthma. Materials and methods. The study enrolled 244 patients with asthma and 60 conditionally healthy subjects. Twenty-five parameters were assessed: expression of interleukin-4 receptors, interleukin-6 receptors (IL-6R), Toll-like receptors (TLR) 2 and 4; the mitochondrial membrane potential coefficient (cMMP) of CD4+ and CD8+ cells; levels of malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), thioredoxin-1 (Trx-1), total antioxidant activity (TAA), glutathione (total, oxidised and reduced), interleukin-4 and interleukin-6; and the fatty-acid composition of leukocyte mitochondrial membranes. Intersystem interactions were analysed with Terentyev’s correlation pleiad method. Results. Application of the Terentyev algorithm identified four groups of the most strongly linked indicators for each asthma cohort. In mild controlled asthma, the predictors were Trx-1 level and the MDA/TAA ratio, whereas in mild partially controlled asthma they were Trx-1 and 8-OHdG levels. In moderate controlled asthma, Trx-1 level and the cMMP of CD4+ cells oc-cupied the central positions within the correlation pleiads. Five predictors were defined for moderate partially controlled asthma: 8-OHdG, cMMP of CD4+ cells, total antioxidant activity, and expression of IL-6R and TLR2 on CD4+ cells. Progression of asthma was accompanied by an increase in the power and robustness of the pleiads. Conclusion. Analysis of intersystem interactions in asthma showed that parameters reflecting the intensity of destructive processes, activation of the inflammatory arm of the immune system and destabilisation of signalling interactions take the leading positions within the pleiads. Disease progression and reduced control destabilise intersystem regulatory processes.