3,4-Methylenedioxymethamphetamine (Ecstasy) Decreases Inflammation and Airway Reactivity in a Murine Model of Asthma

Abstract

Objective: 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is a synthetic drug used recreationally, mainly by young people. It has been suggested that MDMA has a Th cell skewing effect, in which Th1 cell activity is suppressed and Th2 cell activity is increased. Experimental allergic airway inflammation in ovalbumin (OVA)-sensitized rodents is a useful model to study Th2 response; therefore, based on the Th2 skewing effect of MDMA, we studied MDMA in a model of allergic lung inflammation in OVA-sensitized mice. Methods: We evaluated cell trafficking in the bronchoalveolar lavage fluid, blood and bone marrow; cytokine production; L-selectin expression and lung histology. We also investigated the effects of MDMA on tracheal reactivity in vitro and mast cell degranulation. Results: We found that MDMA given prior to OVA challenge in OVA-sensitized mice decreased leukocyte migration into the lung, as revealed by a lower cell count in the bronchoalveolar lavage fluid and lung histologic analysis. We also showed that MDMA decreased expression of both Th2-like cytokines (IL-4, IL-5 and IL-10) and adhesion molecules (L-selectin). Moreover, we showed that the hypothalamus-pituitary-adrenal axis is partially involved in the MDMA-induced reduction in leukocyte migration into the lung. Finally, we showed that MDMA decreased tracheal reactivity to methacholine as well as mast cell degranulation in situ. Conclusions: Thus, we report here that MDMA given prior to OVA challenge in OVA-sensitized allergic mice is able to decrease lung inflammation and airway reactivity and that hypothalamus-pituitary-adrenal axis activation is partially involved. Together, the data strongly suggest an involvement of a neuroimmune mechanism in the effects of MDMA on lung inflammatory response and cell recruitment to the lungs of allergic animals.

Cohabitation with a sick partner increases allergic lung inflammatory response in mice

“…Airway inflammation induced by ovalbumin (OVA) aerosol challenge in OVA-sensitized animals mimicked some pathological characteristics of asthma, e.g., peribronchial edema and increased number of lymphocytes and eosinophils in the bronchoalveolar lavage fluid (Portela et al, 2001(Portela et al, , 2002. These events were augmented by early-life psychological stress (Chida et al, 2007), unpredictable stressor procedures (Datti et al, 2002), foot shock stress (Portela et al, 2001(Portela et al, , 2002 and chemically-induced stressors Stankevicius et al, 2012;Hamasato et al, 2013).…”

Anti-inflammatory, expectorant, and antitussive properties of Kyeongok-go in ICR mice

“…During acute inflammation, marked depletion of mast cells due to increases in mast cell activation, and degranulation in the dermis have been detected, and therefore, the inhibition of mast cell activation has been used as a valuable index to predict the efficacy of anti-inflammatory drugs (Cha et al 2013;Yang et al 2013). Apart from the dermis, it has also been reported that increases in mast cells due to migration from nearby connective tissues have been reported in cases of various allergic respiratory disorders (Dahlin et al 2011;Stankevicius et al 2012). Noticeable migration related increase in the mean number of mast cells in the NH 4 OH control mouse of the NH 4 OH exposure coughing mouse model and significant decreases in the mean infiltrating mast cell counts in the ear dermis were observed, which might have resulted from degranulation as demonstrated in the xylene control of the xylene-induced acute inflammatory mouse ear model.…”

Associations between MDMA/ecstasy use and physical health in a U.S. population-based survey sample

“…Finally, future work can also assess the relationship of ecstasy to immune function, as immune dysfunction is a precursor to many of the health conditions in this study. Evidence from the animal literature indicates that ecstasy reduces markers of inflammation (Stankevicius et al, 2012); however, human studies on the effects of ecstasy on the immune system have yielded mixed results (Connor et al, 2005;Pacifici et al, 2001Pacifici et al, , 2002Szabo, 2015) and some studies have suggested potential physiological harm associated with ecstasy use (Downey and Loftis, 2014;Halpin et al, 2014;Vegting et al, 2016). Hence, researchers should conduct these investigations prudently as the evidence for this potential pathway remains preliminary.…”