No abstract

Exposure to environmental tobacco smoke (ETS) has been shown to increase allergic sensitization and reactivity and there has been some suggestion that the influence of ETS on the allergic response is dissimilar in males and females. It is to be determined whether gender differences exist in the IgE response to ovalbumin (OVA) sensitization following ETS exposure from the neonatal period through adulthood. To address this thesis, we examined gender differences in OVA sensitization of BALB/c mice housed from birth through adulthood under smoking and nonsmoking conditions. At 6 weeks of age (day 0) all mice were injected i.p. with OVA in aluminum hydroxide adjuvant followed by three 20 min exposures to 1% aerosolized OVA between day 14 and 80. There were significantly (p<0.05) more total and OVA specific IgE and IgG1 in the serum of females compared to males. Moreover, these sex responses, along with eosinophilia, were further enhanced in mice exposed to ETS. There were also significantly more IgE positive cells in the lungs of female, but not male, mice exposed to ETS compared with ambient air (p<0.05). There was also an elevation of Th2 cytokines (IL4, IL5, IL10, and IL13) after re-stimulation of lung homogenates following ETS exposure. These data demonstrate that female animals are significantly more susceptible than males to the influence of ETS on the allergic response.

Involuntary inhalation of tobacco smoke has been shown to aggravate the allergic response. Antibodies to fungal antigens such as Aspergillus fumigatus (Af) cause an allergic lung disease in humans. This study was carried out to determine the effect of environmental tobacco smoke (ETS) on a murine model of allergic bronchopulmonary aspergillosis (ABPA). BALB/c mice were exposed to aged and diluted sidestream cigarette smoke to simulate 'second-hand smoke'. The concentration was consistent with that achieved in enclosed public areas or households where multiple people smoke. During exposure, mice were sensitized to Af antigen intranasally. Mice that were sensitized to Af antigen and exposed to ETS developed significantly greater airway hyperreactivity than did mice similarly sensitized to Af but housed in ambient air. The effective concentration of aerosolized acetylcholine needed to double pulmonary flow resistance was significantly lower in Af þ ETS mice compared to the Af þ AIR mice. Immunological data that supports this exacerbation of airway hyperresponsiveness being mediated by an enhanced type 1 hypersensitivity response include: eosinophilia in peripheral blood and lung sections. All Af sensitized mice produced elevated levels of IL4, IL5 and IL10 but no IFN-g indicating a polarized Th2 response. Thus, ETS can cause exacerbation of asthma in ABPA as demonstrated by functional airway hyperresponsiveness and elevated levels of blood eosinophilia.

Respiratory syncytial virus causes mild-to-severe respiratory disease in human infants and young children; a closely related bovine respiratory syncytial virus causes a similar disease pattern in calves. Increased disease severity in atopic children suggests that allergic reactivity may enhance the severity of RSV-induced disease. To examine the association between bovine respiratory syncytial virus (BRSV) infection and allergic reactivity two groups of calves were exposed to aerosolized Micropolyspora faeni (Mf) during an experimental BRSV infection. One group exposed to Mf concurrent with BRSV was challenge-exposed to Mf while infected a second time with BRSV, while the other similarly sensitized and infected group was mock challenged. A control group was exposed only to Mf aerosol and another control group was infected with virus but not exposed to Mf aerosol. Parameters examined included: clinical signs, Mf-specific IgG and IgE, BRSV-specific antibody and IgE, leukotrienes C₄ and B₄ prostaglandins E₂, F_2α and D₂, and lung pathology. While the initial BRSV infection failed to enhance sensitization to inhaled Mf a second BRSV infection excerbated cinical signs resulting from Mf aerosol. Consideration of eicosanoid and antibody profiles together with clinical signs suggests that mechanisms of both type I and type III hypersensitivity were operative during Mf challenge of sensitized calves.

Bovine respiratory syncytial virus (BRSV) infection of calves has been associated with a type-I hypersensitivity syndrome not unlike respiratory syncytial virus-associated pulmonary symptomatology in humans. To study the mechanism of pulmonary pathology in calves and define the relationship with both viral-specific IgE response and IgE titers to concurrent aerosol of Micropolyspora faeni (Mf) we subjected groups of calves to inhalation of Mf during acute BRSV infection. The calves were divided into 4 groups: exposed to virus only (group 1); exposed to aerosolized Mf over a 24-day period and then challenged with Mf during BRSV infection (group 2); similarly exposed to aerosolized Mf and then challenged with Mf without BRSV infection (group 3) and exposed to aerosolized Mf, infected with virus but not challenged with Mf (group 4). All calves were followed for appearance of IgE-specifïc responses to both BRSV and Mf, clinical disease expression, and pulmonary pathology including viral and allergen localization by immunohistology. Our data indicate an association of BRSV-specific IgE with increased development of lung pathology and clinical disease expression and an enhancing effect of aerosolized Mf on induction of virus-specific IgE. The presence of BRSV-specific IgE was solely in calves with the most significant macroscopic and microscopic pneumonic lesions.