ABSTRACT
Neutrophils, known to be mobilized and activated in high amounts through Il-17 stimulation, are a key factor for clinical manifestation and imbalance of redox systems favoring a dominant oxidative state in both severe asthma and acute lung injury (f). The aim of this study was to evaluate in mice, the effect of Secukinumab (SECU) in a model of ovalbumin-induced asthma exacerbated with LPS administration to induce ALI, compared to dexamethasone (DEXA), already known for its benefit in both asthma and ALI. Results on cytokine levels for specific Th1, Th2 and Th17 revealed an interplay of immune responses. For Th1 effector cytokines in BALF, DEXA treatment increased TNF-α levels, but TNF-α was not modified by SECU; DEXA and SECU significantly decreased IFN-γ and IL-6 levels. For typical Th2 cytokines, DEXA significantly increased Il-4, Il-5 and Il-13 levels, while SECU significantly inhibited Il-5 levels. Both SECU and DEXA significantly decreased Il-17 levels. Cytokine level changes in lung tissue homogenate were partly similar to BALF cytokines. Conclusion: in addition to DEXA, SECU possesses the ability to modulate inflammatory cytokine release and to decrease Th17 responses in ALI overlapped on exacerbated asthma in mice.
ABSTRACT
One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets. On the other hand, in the last decade, many studies described the potentially anti-inflammatory effects of marine-derived biologically active compounds. Analyzing the underlying anti-inflammatory mechanisms of action for these marine-derived biologically active compounds, we observed some of the targeted pathogenic molecular mechanisms similar to those described in glucocorticoid (GC) resistant asthma. This article gathers the marine-derived compounds targeting pathogenic molecular mechanism involved in GC resistant asthma and provides a basis for the development of effective marine-derived drugs.
