Lactoferrin Ameliorates Ovalbumin-Induced Asthma in Mice through Reducing Dendritic-Cell-Derived Th2 Cell Responses

Abstract

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.

Exploring the Role of Lactoferrin in Managing Allergic Airway Diseases among Children: Unrevealing a Potential Breakthrough

“…In vitro LF influenced T-cell differentiation in the spleen, increasing the number of regulatory T cells (Foxp3+) and decreasing Th2-associated IL-4+ T cells, which suggests a shift towards a less allergic, more regulated immune response. It also led to the reduced expression of CD80 and CD86 on dendritic cells, suggesting inhibited DC activation and a shift toward a less allergic immune response [ 144 ]. In addition to the effects of LF on the allergic inflammatory cascade, two highly similar studies assessed the impact of milk-derived hLF on inflammation induced by oxidative stress in ragweed allergen-induced allergic asthma, utilising human respiratory epithelial cells in vitro and murine models in vivo.…”

Potential of Lactoferrin in the Treatment of Lung Diseases

“…Given before sensitization, LF prevented inflammation, while given during it reduced the process [ 119 , 120 ]. In a similar vein, a recent study found that in an ovalbumin (OVA) mice model of asthma, oral LF during sensitization abolished airway hyperreactivity and inflammation by decreasing the elevated levels of TNF-α, IL-4, IL-5, IL-13 and increasing the downregulated levels of the anti-inflammatory IL-10 in BALF [ 121 ].…”