Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

Abstract

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations

“…It also has anti-inflammatory and anti-oxidant [3, 4] and anti-bacterial and anti-viral properties [2, 5]. Recently, ambroxol was shown to also exhibit immunomodulatory effects in a murine asthma model, where it normalized airway hyperresponsiveness and reduced eosinophils and Th2-related cytokines in bronchoalveolar lavage [6]. Finally, ambroxol affects lysosomal function, which may be beneficial in lysosomal storage diseases [7] or Parkinson’s disease [8], but the relevance of this finding remains to be tested clinically.…”

Ambroxol for the treatment of fibromyalgia: science or fiction?

“…Interestingly, overall this had a beneficial and protective effect. 285 This applies similarly to IL5, which has a positive chemotactic action on eosinophilic granulocytes: Sturgill et al 287 also demonstrated a reduction of IL5 in FMS. Ambroxol also has an inhibiting effect concerning IL5, and if administered prior to provocation in an animal model, suppressed hyperreactivity and airway eosinophilia and reduced inflammation of subepithelial regions.…”

“… 87 Following exposure to allergens in an artificially sensitized respiratory tract in an animal model, however, ambroxol induced an increase in IL10 in a “protective” manner. 285 …”

“…Ambroxol also has an inhibiting effect concerning IL5, and if administered prior to provocation in an animal model, suppressed hyperreactivity and airway eosinophilia and reduced inflammation of subepithelial regions. 285 The relationships described raise the question of whether potent inhibition of the release of IgE-dependent mediators 294 and immunomodulatory cytokines from basophilic granulocytes by ambroxol, 54 as well as the immunomodulatory significance of Na v 1.8 sodium-channel inhibition by ambroxol, 295 are important in FMS and warrant further investigation.…”

Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for?

“…A co-aerosolized, DPPC-ambroxol intervention may present a synergistic outcome in ARDS intervention at early stages and may be a potential clinical trial candidate for COVID-19 as it may essentially provide with alleviation of the inherent inflammatory response, attenuation of epithelial cell damage, decreased interstitial exudation and edema, and hence reduced lung damage. When co-administered, ambroxol may act by reducing the inflammation (Takeda et al, 2016;Kanie et al, 2017) which in turn may minimize the pulmonary capillary permeability thereby affecting the edema blebs (Figure 1). Concurrently, the exogenous surfactant delivered to the lungs may replenish the deactivated surfactant and hence the surfactant lining will be restored.…”