Chronic inflammation in asthma: a contest of persistence vs resolution

Abstract

Recent investigations have highlighted that endogenous anti‐inflammatory mediators and immune regulating mechanisms are important for the resolution of inflammatory processes. A disruption of these mechanisms can be causally related not only to the initiation of unnecessary inflammation, but also to the persistence of several chronic inflammatory diseases. In asthma, chronic Th‐2 driven eosinophilic inflammation of the airways is one of the central abnormalities. To date, elucidating the role of the different pro‐inflammatory mediators involved in orchestrating the inflammatory processes in asthma has been the subject of intense research in both humans and animal models. However, the counter‐regulatory mechanisms that co‐determine the outcome in the contest of resolution vs persistence of the eosinophilic airway inflammation remain poorly understood. These are currently being investigated in animal models of chronic asthma. Elucidating these mechanisms is of relevance, since it can give rise to a new therapeutic approach in the treatment of chronic airway inflammation in asthmatics. This novel concept of treatment involves the stimulation of endogenous anti‐inflammatory pathways, rather than solely antagonising the various pro‐inflammatory mediators. Here, we review and discuss the current knowledge about these endogenous anti‐inflammatory mediators in clinical and experimental asthma.

Impairment of phagocytosis of apoptotic cells and its role in chronic airway diseases

“…Asthma is a complex syndrome with a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation [82,83]. Tissue damage and increased apoptotic rates with typical TUNEL and caspase-3 positively stained epithelial cells and smooth muscle cells were observed in the proximal conducting airways and in the central bronchus of patients with severe disease, while in patients with intermittent stage of the disease apoptosis rates were comparable to controls [84].…”

Hydrogen Peroxide in Inflammation: Messenger, Guide, and Assassin

“…Failure to resolve an immune response can also cause severe tissue damage, due to persistent degranulation, and may lead to chronic inflammation, which ceases to be beneficial to the host. Overall, inflammation is now recognised as a central feature of prevalent pathologies, such as atherosclerosis, cancer, asthma, thyroiditis, inflammatory bowel disease, autoimmune disease, as well as Alzheimer's and Parkinson's disease [4–6]. Hence, the regulation of an inflammatory response is an active field of research.…”

Interacting mast cells and eosinophils acquire an enhanced activation state in vitro

“…As we have mentioned, inhibiting outcomes are also plausible, as MCs and Eos have inhibitory surface molecules and immunoregulatory properties . If such negative signals exist in the AEU, they may be initially overpowered by stimulatory pathways yet come to play later within allergic resolution . Future studies should reveal the AEU effects on MC/Eos responsiveness in diverse conditions.…”