Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.

Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early markers of WPS exposure that precede airway dysfunction. Our data provide information on the initial steps involved in the respiratory effects of WPS, which constitute the underlying causal chain of reactions leading to the long-term effects of WPS.

Attenuated EAN in TNF-α deficient mice is associated with an altered balance of M1/M2 macrophages.

The role of tumor necrosis factor (TNF)-α and its receptors in neuroautoimmune and neuroinflammatory diseases has been controversial. On the basis of our previous studies, we hereby aimed to further clarify TNF-α's mechanism of action and to explore the potential role of TNF-α receptor (TNFR)1 as a therapeutic target in experimental autoimmune neuritis (EAN). EAN was induced by immunization with P0 peptide 180-199 in TNF-α knockout (KO) mice and anti-TNFR1 antibodies were used to treat EAN. Particularly, the effects of TNF-α deficiency and TNFR1 blockade on macrophage functions were investigated. The onset of EAN in TNF-α KO mice was markedly later than that in wild type (WT) mice. From day 14 post immunization, the clinical signs of TNF-α KO mice were significantly milder than those of their WT counterparts. Further, we showed that the clinical severity of WT mice treated with anti-TNFR1 antibodies was less severe than that of the control WT mice receiving PBS. Nevertheless, no difference with regard to the clinical signs of EAN or inflammatory infiltration in cauda equina was seen between TNF-α KO and WT mice with EAN after blockade of TNFR1. Although TNF-α deficiency did not alter the proliferation of lymphocytes in response to either antigenic or mitogenic stimuli, it down-regulated the production of interleukin (IL)-12 and nitric oxide (NO), and enhanced the production of IL-10 in macrophages. Increased ratio of regulatory T cells (Tregs) and reduced production of interferon (IFN)-γ in cauda equina infiltrating cells, and elevated levels of IgG2b antibodies against P0 peptide 180-199 in sera were found in TNF-α KO mice with EAN. In conclusion, TNF-α deficiency attenuates EAN via altering the M1/M2 balance of macrophages.

Evaluation of the pulmonary effects of short-term nose-only cigarette smoke exposure in mice.

Much is known about the chronic effects of cigarette smoke (CS) on lung function and inflammation and development of chronic obstructive pulmonary disease. However, the underlying pathophysiological mechanisms related to the short-term exposure to CS are not fully understood. Here, we assessed the effect of CS generated by nine consecutive cigarettes per day for four days in a nose-only exposure system on airway resistance measured using forced oscillation technique, lung inflammation and oxidative stress in BALB/c mice. Control mice were exposed to air. Mice exposed to CS showed a significant increase of neutrophils and lymphocytes numbers in bronchoalveolar lavage (BAL). The total protein and endothelin levels in BAL fluid were significantly augmented suggesting an increase of alveolar-capillary barrier permeability. Similarly, airway resistance was significantly increased in the CS group compared with controls. Furthermore, reactive oxygen species and lipid peroxidation levels in lung tissue were significantly increased. The antioxidant activities of reduced glutathione, glutathione S transferase and superoxide dismutase were all significantly increased following CS exposure, indicating that CS could trigger adaptive responses that counterbalance the potentially damaging activity of oxygen radicals induced by CS exposure. In conclusion, our data indicate that short-term nose-only exposure to CS causes lung inflammation and increase of airway resistance mediated at least partly through the oxidative stress.