The incidence of hypersensitivity pneumonitis (HP) is lower in smokers than in nonsmokers. Because nicotine is immunosuppressive, we hypothesized that it could have a protective effect on HP induction in vivo. HP was induced in mice that were treated with nicotine either intraperitoneally (IP) (0.5 to 2.0 mg/kg/day) or intranasally (IN) (0.025 to 2.0 mg/kg/day). Both IP- and IN-treated animals had fewer bronchoalveolar lavage total cells and lymphocytes and a decreased lung tissue inflammation. IFN-gamma but not interleukin-10 mRNA expression was reduced in lung tissue of 2.0-mg/kg IN-treated animals. To test the effect of nicotine on alveolar macrophages, AMJ2-C11 cells were treated with nicotine and stimulated with lipopolysaccharide or Saccharopolyspora rectivirgula, a causative agent of HP. Nicotine reduced tumor necrosis factor release and tumor necrosis factor, interleukin-10, and IFN-gamma mRNA expression after stimulation and decreased CD80 expression by 55% in lipopolysaccharide-stimulated cells and by 41% in S. rectivirgula-stimulated cells. We conclude that nicotine could be, at least in part, responsible for the protection observed in smokers against HP. The inhibitory effect of nicotine on alveolar macrophages could be one of the mechanisms involved.

Exposure to swine confinement buildings has a negative impact on respiratory health. A short exposure to this environment results in an acute airway inflammatory response. The present study was performed to confirm and further define the acute effects of working in a swine building, and to determine whether these effects are reproducible.Seven previously nonexposed normal subjects underwent evaluations that included hourly measurement of forced expiratory volume in one second (FEV1), methacholine challenge (the provocative concentration producing a 20% fall in FEV1 (PC20)), bronchoalveolar lavage (BAL), nasal lavage (NL), and blood analyses, before (control) and after each of two 5 h exposures to a swine building environment. The exposures were conducted 8 days apart. The levels of total dust, endotoxins, and ammonia (NH 3 ) in the confinement building were measured on each day of exposure.Both In normal naive subjects, repeated exposure to the environment of a swine building induced a marked and reproducible reduction in forced expiratory volume in one second, increase in airway responsiveness, and increased neutrophilic inflammatory response. These results could not be accounted for by any of the environmental factors measured.

Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have antiinflammatory properties and in some instances smooth muscle relaxing effects. Since inflammation and airway smooth muscle contraction are two major components of asthma, the present authors investigated the effects of DMPP on airway inflammation and airway resistance in a mouse model of asthma.Mice were sensitised and challenged with ovalbumin (OVA) and treated either intraperitoneally or intranasally with DMPP. The effect of DMPP was tested on airway inflammation, airway resistance and on the increase of intracellular calcium in bronchial smooth muscle cells.DMPP given either during sensitisation, OVA challenges or throughout the protocol prevented lung inflammation and decreased the serum level of OVA specific immunoglobulin E. DMPP administration reduced the number of total cells, lymphocytes and eosinophils in the bronchoalveolar lavage (BAL) fluid. Intranasal DMPP administration was as effective as dexamethasone (DEXA) in reducing total cell count and eosinophil counts in BAL fluid. DMPP, but not DEXA, reduced tissue inflammation. Intranasal DMPP, given 10 min before the test, reduced airway responsiveness to metacholine. DMPP also reduced the increase in intracellular calcium in response to bradykinin.In conclusion, these results show that 1,1-dimethyl-4-phenylpiperazinium reduces lung inflammation and prevents airway hyperresponsiveness in the mouse model of asthma.

Hypersensitivity pneumonitis (HP) is characterised by lung lymphocytosis. Most individuals exposed to HP antigens remain asymptomatic. The mechanisms involved in the impaired immune tolerance leading to HP are unclear. Normally, T-regulatory (Treg)-cells control the immune response. The aim of the present study was to determine whether Treg-cell suppressive function deficiency can explain the uncontrolled inflammation in HP.Bronchoalveolar lavage (BAL) and blood samples were obtained from normal subjects, asymptomatic individuals and HP patients. BAL and blood Treg-cells were isolated. The ability of Treg-cells to suppress T-cell proliferation and the role of interleukin (IL)-17 was verified.BAL and blood Treg-cells from normal subjects suppressed the proliferative response of activated T-cells by 47.1 and 42%, respectively. BAL and blood Treg-cells from asymptomatic subjects had a slightly decreased activity and suppressed proliferation by 29.4 and 31.8%, respectively. BAL and blood Treg-cells from HP patients were totally nonfunctional and unable to suppress proliferation. Low levels of IL-17 were detected in sera and BAL from both normal and asymptomatic individuals, whereas measurable levels were found in patients.Treg-cells may be involved in antigen tolerance in asymptomatic subjects. Defective Treg-cell function, potentially caused by increased IL-17 production, could account for the exacerbated immune response characteristic of HP.