Bronchial asthma (BA) is the most widespread chronic inflammatory disease. Since BA is associated with a systemic inflammation state, a comprehensive study of its effect in this disease, and influence of pathogenetic therapy should be performed, by studying the whole blood cytokine status of the patients suffering with BA. The cells from respiratory tract in acute-phase BA patients may produce pro-, as well as anti-inflammatory mediators. The anti-inflammatory mediators are able to suppress activity of immune cells in peripheral blood. Thus, the aim of present study was to evaluate eventual inflammation-associated and functional activity of immune cells from the patients’ peripheral blood in BA and following appropriate therapy. Bacterial lipopolysaccharide (LPS) a classical pro-inflammatory agent. We have studied an LPSinduced cytokine-induced ex vivo secretion model by peripheral blood immune cells, as a relevant test for their functional activity. The LPS-induced responses of whole blood cells from patients with proven BA diagnosis have been studied at pre-treatment time points, and following two weeks of basic anti-inflammatory therapy. According to clinical indications, the antagonists of CysLTR1, or combinations of glucocorticosteroids and β-adrenoreceptor agonists were administered by inhalation to BA patients. LPS-induced production of TNFα, IL-6, IL-8 (at 6 h) and IFNγ, IL-17A or IL-1β (at 24 h) by whole blood cells from BA patients or healthy volunteers has been assessed by ELISA technique. The cytokine production from non-stimulated whole blood cells from BA patients and healthy volunteers were used as the baseline control. IL-4 concentrations in plasma of BA patients and healthy volunteers were also measured. We have shown a decrease of IL-6 production in control blood samples from BA patients after two weeks of therapy. This may indicate the attenuation of the observed inflammatory process. The therapy applied did not influence the background levels and LPS-induced secretion of IL-1β, IL-1ra, IFNγ, and IL-8 in whole blood samples from BA patients. IL-4 plasma levels in BA patients were not changed after two weeks of therapy. It has been shown that whole blood from BA patients produced less TNFα and IL-8, both in control samples, and during their response to LPS, than the values obtained in healthy volunteers. These findings are in agreement with a notion that BA causes partial depression of innate immune cells activity. The increased LPS-induced TNFα secretion by the whole blood cells from BA patients has been observed following two weeks of basic anti-inflammatory therapy. We suggest that the increased LPS-induced TNFα secretion could be explained by partial restoration of peripheral blood immune cell activity associated with anti-inflammatory BA therapy. To elucidate the mechanism of increased LPS-induced TNFα secretion, we have estimated whole blood concentration of soluble CD14 (sCD14) in BA patients. No significant differences between sCD14 concentrations have been found. Obtained result presume existence of sCD14-independent mechanism of TNFα regulation by whole blood cells in response on LPS which may occur during anti-inflammatory therapy of BA. We suppose that basic anti-inflammatory therapy of BA does not simply reduce IL-6 concentration in peripheral blood, but may also partially restore the activity of innate immune cells in BA patients.
The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke
