Interference of methysergide, a specific 5-hydroxytryptamine receptor antagonist, with airway chronic allergic inflammation and remodelling in a murine model of asthma.

BACKGROUND: Airway remodelling encompasses the structural changes observed in asthmatic airways. Mast cells, through the release of histamine and 5-hydroxytryptamine (serotonin), are implicated in early asthmatic reactions, bronchoconstriction and mucosal oedema, and in the development of bronchial hyperresponsiveness. However, the association between serotonin and remodelling processes in murine model of airways inflammation remains to be elucidated. OBJECTIVE: As serotonin is released by murine mast cells upon antigen challenge, we tested the hypothesis of its involvement in the development of inflammatory and remodelling processes in a murine model of chronic airway inflammation following prolonged allergen challenge. Methods BALB/c mice were exposed to aerosolized ovalbumin for 20 min 2 days a week, for 4 consecutive weeks. Two hours before each challenge, they were treated with methysergide (intranasally, 40 microg/kg). Forty-eight hours after the last aerosol challenge, bronchoalveolar lavage (BAL) and lung tissue were collected for analysis. RESULTS: Methysergide inhibited the allergen-induced increase in airway eosinophilia, reduced T helper type 2 (Th2) cytokines in lung, spleen or thoracic lymph nodes, and specific IgE levels. The extravasation of plasma and fibronectin production in the lung, and collagen deposition in the lung were also inhibited after methysergide treatment. Although methysergide treatment induced an increase in IFN-gamma levels, experiments with neutralizing antibody suggest that this is not responsible for inhibition. In addition, instillation of serotonin to immunized mice induced eosinophil recruitment to BAL, Th2 cytokine production and fibronectin release in lung as well as collagen deposition. CONCLUSION: Serotonin may contribute to the development and maintenance of remodelling through the release of cytokines and of fibrogenic mediators. Serotonin should therefore be considered as relevant for the development and maintenance of airway remodelling.

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties

Adult Ascaris suum body extract (Asc) prepared from male and female worms (with stored eggs) down-regulates the specific immune response of DBA/2 mice to ovalbumin (OA) and preferentially stimulates a Th2 response to its own components, which is responsible for the suppression of the OA-specific Th1 response. Here, we investigated the participation of soluble extracts prepared from male or female worms or from eggs (E-Asc) in these immunological events. Extracts from either sex (1 mg/animal) or E-Asc (0.35 or 1 mg protein/animal) suppressed the delayed-type hypersensitivity (DTH) reaction (60-85 percent), proliferative response (50-70 percent), IL-2 and IFN-gamma secretion (below detection threshold) and IgG1 antibody production (70-90 percent) of DBA/2 mice to OA. A dose of 0.1 mg E-Asc/animal did not change DTH or proliferation, but was as effective as 0.35 mg in suppressing IL-2 and IFN-gamma, and OA-specific IgG1 antibodies. Lymph node cells from DBA/2 mice injected with Asc (1 mg/animal) or a high dose of E-Asc (1 mg protein/animal) secreted IL-4 upon in vitro stimulation with concanavalin A. As previously demonstrated for Asc, the cytokine profile obtained with the E-Asc was dose dependent and changed towards Th1 when a low dose (0.1 mg protein/animal) was used. Taken together, these results suggest that adult worms of either sex and eggs induce the same type of T cell response and share similar immunosuppressive properties

Extracts of Ascaris suum egg and adult worm share similar immunosuppressive properties.

Adult Ascaris suum body extract (Asc) prepared from male and female worms (with stored eggs) down-regulates the specific immune response of DBA/2 mice to ovalbumin (OA) and preferentially stimulates a Th2 response to its own components, which is responsible for the suppression of the OA-specific Th1 response. Here, we investigated the participation of soluble extracts prepared from male or female worms or from eggs (E-Asc) in these immunological events. Extracts from either sex (1 mg/animal) or E-Asc (0.35 or 1 mg protein/animal) suppressed the delayed-type hypersensitivity (DTH) reaction (60-85%), proliferative response (50-70%), IL-2 and IFN-gamma secretion (below detection threshold) and IgG1 antibody production (70-90%) of DBA/2 mice to OA. A dose of 0.1 mg E-Asc/animal did not change DTH or proliferation, but was as effective as 0.35 mg in suppressing IL-2 and IFN-gamma, and OA-specific IgG1 antibodies. Lymph node cells from DBA/2 mice injected with Asc (1 mg/animal) or a high dose of E-Asc (1 mg protein/animal) secreted IL-4 upon in vitro stimulation with concanavalin A. As previously demonstrated for Asc, the cytokine profile obtained with the E-Asc was dose dependent and changed towards Th1 when a low dose (0.1 mg protein/animal) was used. Taken together, these results suggest that adult worms of either sex and eggs induce the same type of T cell response and share similar immunosuppressive properties.