Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma

Abstract

Asthma is one of the most common chronic airway inflammatory diseases. The clinical hallmarks of asthma include elevated serum levels of immunoglobulin E (IgE), eosinophilic inflammation and airway hyper-responsiveness (AHR). Arsenic trioxide (As 2 O 3 ) is considered a carcinogen; however, it has also been used to treat diseases, such as syphilis, in traditional Chinese and Western medicine. Today, As 2 O 3 is used as one of the standard therapies for acute promyelocytic leukemia (APL). Previous studies have indicated that As 2 O 3 can induce apoptosis in eosinophils. However, the effect of As 2 O 3 on asthma has not been investigated. We used ovalbumin (OVA)-immunized mice as a model for asthma and treated mice with As 2 O 3 at doses of 2.5 and 5 mg/kg. The mice were then monitored for OVA-specific IgE production, airway inflammatory cell infiltration and AHR. We found that administration of As 2 O 3 in OVA-immunized mice abrogated airway eosinophil recruitment by downregulating eotaxin expression but did not alter serum IgE or IL-5 levels in bronchoalveolar lavage fluid (BALF). Furthermore, the development of AHR and cellular infiltration into the airway were reduced by treating mice with As 2 O 3 . In vitro data suggested that low concentrations of As 2 O 3 could induce only a small degree of apoptosis in primary pulmonary cells but could significantly inhibit the secretion of eotaxin by these cells. These results indicate that the administration of As 2 O 3 to OVA-immunized mice can suppress lung allergic inflammatory responses. As 2 O 3 might therefore have therapeutic potential in treating allergic airway inflammatory diseases.

Effect of therapeutic arsenic exposure on pulmonary function

“…Thirdly, the therapeutic use of arsenic in the formulation known as "Fowler's solution", first recognized in the London Pharmacopoeia of 1890, was well-known for treating severe asthma as indicated in the 11th edition (in 1989) Merck index [14,33]. Interestingly, recent animal models have also suggested a therapeutic role of arsenic trioxide in alleviating airway hyperresponsiveness and eosinophilia [34,35]. Therefore, the short-term therapeutic use of arsenic trioxide as in our cohort may even potentially improve the pulmonary function.…”

Old dog, new trick: Trivalent arsenic as an immunomodulatory drug

“…For basophils, the direct effects of As(III) have not yet been investigated. However, activation of basophils may be impaired in vivo during As(III) administration, because levels of IgE, an important driver of basophil activation, were decreased in the BALF of As 2 O 3‐ treated mice (Chu et al, 2010; Zhou et al, 2006). For mast cells, it was reported that NaAsO 2 inhibits anti‐IgE stimulated degranulation via suppression of early tyrosine phosphorylation (Hutchinson et al, 2011).…”

Activation of integrated stress response pathway regulates IL‐1β production through posttranscriptional and translational reprogramming in macrophages

“…In addition, it has been demonstrated that arsenite influences various cellular processes like apoptosis, proliferation, inflammation, angiogenesis, and immune response . Therapeutically, arsenic compounds have often been used in traditional Chinese and Western medicine for decades to treat several diseases including tooth diseases, rheumatosis, psoriasis, syphilis, and trypanosomiasis . Arsenic compounds have shown remarkable potency against acute promyelocytic leukemia and have become one of the standard therapies for acute promyelocytic leukemia .…”