The review considers the main points of the concept of progressive chronic heart failure (CHF). The neurohumoral model of CHF pathogenesis could create novel approaches to treating these patients. However, recent studies have shown that the ways of activating the neurohumoral systems in CHF are much more complex. The increased local synthesis of hormones causes the activation of proinflammatory cytokines and proto-oncogenes, which have a number of negative effects. Multiple studies have formulated the immunoinflammatory concept of CHF pathogenesis, according to which the increased concentration of interleukin-6 is a marker of poor prognosis in CHF, and the level of tumor necrosis factor-α directly correlates with the severity of its clinical manifestations and the activity of the neurohumoral background in decompensation. The review gives a classification of cytokines and describes the reasons for their elevated plasma concentration, their possible role in the occurrence and progression of CHF, and their prognostic significance. The pathogenesis of CHF, which includes cytokine aggression, requires further studies of the effect of the inflammatory component on the course of heart failure.
Background
There is still insufficient knowledge with regard to the potential involvement of mast cells (MCs) and their mediators in the pathology of coronavirus disease-2019 (COVID-19). Therefore, our study aimed to investigate the role of MCs, their activation and protease profiles in the pathogenesis of early and late lung damage in COVID-19 patients.
Methods
Formalin-fixed and paraffin embedded lung specimens from 30 patients who died from COVID-19 and 9 controls were used for histological detection of MCs and their proteases (tryptase, chymase) followed by morphometric quantification.
Results
Our results demonstrated increased numbers of MCs at early stage and further augmentation of MCs number during the late stage of alveolar damage in COVID-19 patients, as compared to the control group. Importantly, the percentage of degranulated (activated) MCs was higher during both stages of alveolar lesions in comparison to the controls. While there was no prominent alteration in the profile of tryptase-positive MCs, our data revealed a significant elevation in the number of chymase-positive MCs in the lungs of COVID-19 patients, compared to the controls.
Conclusions
MCs are characterized by dysregulated accumulation and increased activation in the lungs of patients suffering from COVID-19. However, future profound studies are needed for precise analysis of the role of these immune cells in the context of novel coronavirus disease.
CP incorporation into the combination therapy of asthmatic patients contributes to elimination of prooxidant-antioxidant imbalance, which is followed by a marked positive clinical effect.
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