Mast cell stabilizers as a supportive therapy can contribute to alleviate fatal inflammatory responses and severity of pulmonary complications in COVID-19 infection

Abstract

SARS-CoV-2(COVID-19) leads to severe acute respiratory syndrome by settling the pulmonary system. Mast cells (MCs) are multifunctional immune cells that are extensively distributed throughout the body and mostly present in pulmonary system. MCs play a vital role in acquired and innate immunity, and to maintain immune homeostasis of the body through a wide range of mediators in their cytoplasmic granules. Severe acute respiratory syndrome with proinflammatory cytokine release and pneumonia during COVID-19 infection can result in the death, in particular in debilitated individuals or those suffering from related chronic disorders. In this review, we attempt to discuss potential relationship between COVID-19 symptoms and mast cells as well as potential use of mast cell stabilizers as a supportive therapeutic option in COVID-19 infection. MCs are main source of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α as well as bronchoconstrictor mediators such as histamine, prostaglandin-D2 and leukotriene-C4 that can lead to fatal inflammatory responses and pulmonary complications during COVID-19 infection. SARS-CoV-2 may activate MCs through toll-like receptors or by inducing the crosslinking of the IgE-FcεRI, thus leading to release of those mediators. SARS-CoV-2-induced abnormal production and release of these mediators from MCs can further exacerbate inflammation in respiratory system, consequently pulmonary complications. Therefore administration of MC stabilizers as a supportive therapy may be useful to alleviate inflammatory responses and pulmonary complications in order to reduce deaths from SARS-CoV-2 infection.

Non‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19

“…These studies thus suggest that targeting the PGD 2 – DP1 receptor pathway may be helpful to control SARS‐CoV infection in older humans. Furthermore, SARS‐CoV‐2 may cause mast cell activation via the toll‐like receptors (TLRs) or inducing crosslink of IgE–FcεRI and subsequent production of PGD 2 , where use of mast cell stabilisers, including β‐adrenoceptor agonists, is highlighted as potential therapeutic targets during SARS‐CoV‐2 infection due to their efficient inhibition of PGD 2 release (Kilinç & Kilinç, 2020). Infection with respiratory syncytial virus (RSV) up‐regulates HPGDS expression and increases PGD 2 secretion by cultured human primary airway epithelial cells (Werder et al, 2018).…”

Prophylactic or therapeutic administration of Holarrhena floribunda hydro ethanol extract suppresses Complete Freund’s Adjuvant-induced arthritis in Sprague-Dawley rats    

“…Histamine involvement in COVID-19 progression has been suggested and/or described in several reports (P. J. Barnes, 1991;Hill, 1992;Kilinc et al, 2020;Kritas et al, 2020). The anti-histaminic potential of HFE, again demonstrated in this study by HFE inhibition of both acute and chronic oedema due to CFA, could play a role in modulating the dysregulated immune response in COVID-19.…”

Hydro ethanol extract of Holarrhena floribunda stem bark exhibits anti-anaphylactic and anti-oedematogenic effects in murine models of acute inflammation

“…Histamine plays a central role in acute in ammation and anaphylaxis (Branco et al, 2018) ( Winbery & Lieberman, 2002). Relevant to COVID-19, histamine release from mast cells is known to mediate bronchoconstriction (Barnes, 1991;Hill, 1992;Kilinc et al, 2020;Kritas et al, 2020), and has been implicated in the progression of oedema observed in COVID-19 pulmonary disease (Malone et al, 2020).…”