Inhibition of Virus-Induced Cytokine Production from Airway Epithelial Cells by the Late Addition of Budesonide

Abstract

Background and objectives: Viral infection is the main cause of asthma and COPD (chronic obstructive pulmonary disease) exacerbation and accumulate inflammatory cells to airway tissue. We have reported poly I:C, a mimic product of the virus and ligand of toll-like receptor 3 (TLR3), induced inflammatory chemokines from airway epithelial cells and found prior incubation with corticosteroids diminishes the effect of TLR3 activation. In clinical practice, mild asthma is recommended as-needed budesonide (BUD) when symptoms occur following a viral infection, etc. However, many questions still surround BUD’s usefulness if taken after a virus has already infected airway tissue. The aim of this study was to investigate the inhibitory effects of BUD on inflammatory cytokines induced by viral infection. Materials and Methods: Normal human bronchial epithelial (NHBE) cells were stimulated with poly I:C or infected with human rhinovirus-16 (HRV16) and BUD was added after the initial stimulation. Expression of both thymic stromal lymphopoietin (TSLP) and CCL26/eotaxin-3 was quantified by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Knockdown study was performed. Results: Pre-or post-incubation with BUD inhibited both poly I:C- and HRV16-induced mRNAs and proteins of both thymic stromal lymphopoietin (TSLP) and CCL26 with significance. Knockdown of the glucocorticoid receptor diminished these effects of BUD. Under the same conditions of BUD’s experiment, post-incubation with neither fluticasone propionate nor dexamethasone suppressed expression of both TSLP and CCL26, which induced by poly I:C. Conclusion: Post-addition of BUD inhibited the virus-induced TSLP and CCL26 from the airway epithelial cells. These results suggest that inhalation of BUD after viral infection has beneficial effects on asthma. Conclusion: Late addition of BUD may benefit among patient with viral infection and type 2 allergic airway disease such as asthma.

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…Hydrocortisone showed to improve respiratory and mortality outcome in bacterial severe community-acquired pneumonia [34] and inconstant efficacy in septic shock [35,36]. Budesinide might reduce post viralinflammatory-cytokine production by human bronchial epithelial cells in vitro [37], while discordant results are reported in viral influenza pneumonia.…”

Virus-Induced Asthma Exacerbations: SIRT1 Targeted Approach

“…Current knowledge suggests that airway epithelial damage triggered by viral infections promotes the production of IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), which in turn leads to the activation of ILC2 and exacerbation of asthma [102]. We showed that the late addition of budesonide attenuates the increase in TSLP caused by viral infection [19]. Although Tezepermab, a biologic that targets TSLP for treatment, was reported to reduce the frequency of asthma exacerbations [108], the role of ILCS2, including IL25 and IL-33, is not fully understood, and we need to elucidate the full mechanism of its production and develop new treatment options.…”

“…They demonstrated that patients with higher FeNO levels had significantly shorter time to arrive at asthma exacerbation than those patients with lower FeNO [69]. Activation of toll-like receptor 3 (TLR3), a virus receptor within the airway epithelial cells, led to the induction of eosinophil-attracting chemokines (CCL11, eotaxin) in the cellular bases [18][19][20][21][22]. These findings suggested that eosinophilic airway inflammation is an important aspect of virus-induced asthma exacerbation.…”

“…In addition to the viral infections themselves, it has been suggested that viral infections can reduce the species, numbers, and diversity of microbiota, so-called dysbiosis [17], indicating that asthma is a very complex disease. Viral infection, which can affect patients with both phenotypes, induces the formation of a wide range of cytokines and chemokines in the airway [18][19][20][21][22]. Eosinophils, T helper-2 (Th2) lymphocytes, type 2 innate lymphoid cells (ILC2), Th17 cells, and neutrophils are involved in epithelial chemokine production in virus-induced asthma exacerbation [18][19][20][21][22] (Figure 1).…”

“…Viral infection, which can affect patients with both phenotypes, induces the formation of a wide range of cytokines and chemokines in the airway [18][19][20][21][22]. Eosinophils, T helper-2 (Th2) lymphocytes, type 2 innate lymphoid cells (ILC2), Th17 cells, and neutrophils are involved in epithelial chemokine production in virus-induced asthma exacerbation [18][19][20][21][22] (Figure 1). Inhaled corticosteroids (ICS), which have been used widely for treating asthma over the past few decades, inhibit the expression of inflammatory cytokines in the airway during virus-induced asthma exacerbations, especially Th2-airway inflammation [23].…”