title: Altered innate immune response in farmers and smokers.
abstract: Pig farmers and cigarette smokers are continuously exposed to pathogen-associated molecular patterns (PAMPs) have an increased prevalence of respiratory disorders, such as chronic bronchitis and chronic obstructive pulmonary decease (COPD). We hypothesized that markers of innate immunity, T-helper (Th) cell cytokine profile and acute responses to pro-inflammatory stimuli differ between smokers and farmers, who are exposed to organic material on a daily basis and healthy non-exposed subjects. Eleven non-smoking pig farmers, 12 non-farming smokers and 12 controls underwent bronchial lipopolysaccharide (LPS) challenge and exposure in a pig barn during 3 h on separate days. Toll-like receptor 2 (TLR2), TLR4 and CD14 on blood monocytes and neutrophils and intracellular cytokine profile of Th cells were assessed before and 7 h after exposures. The same outcomes were analysed on peripheral blood and purified neutrophils from farmers and controls after stimulation ex vivo with dust from a pig barn and LPS. Circulating neutrophils and IL-13 and IL-4 producing Th cells were increased in smokers and farmers and TLR2 expression on blood monocytes was decreased in farmers compared with controls and smokers. After in vivo exposure, altered TLR expression was only observed in controls and the ex vivo stimulations showed an attenuated response in farmers compared to the control group. The inflammatory systemic response to pro-inflammatory stimuli is altered in farmers and smokers probably because of adaptive mechanisms arising from chronic exposure to organic material. This increased proportion of Th2 cells and reduced TLR2 expression may have health-related implications and may be related to the increased prevalence of respiratory disorders observed in these groups.
authors.affiliation: Lung and Allergy Research, National Institute of Environmental Medicine Karolinska Institutet, Stockholm, Sweden. karin.sahlander@ki.se
authors.forename: Karin
authors.initials: K
authors.lastname: Sahlander
authors.forename: Kjell
authors.initials: K
authors.lastname: Larsson
authors.forename: Lena
authors.initials: L
authors.lastname: Palmberg
mesh_terms: D000328:Adult; D000368:Aged; D001985:Bronchial Provocation Tests; D029481:Bronchitis, Chronic / Q000453:epidemiology / Q000209:etiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects*; D052638:Particulate Matter / Q000008:administration & dosage / Q000009:adverse effects*; D015995:Prevalence; D012907:Smoking / Q000009:adverse effects*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D052638:Particulate Matter; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015847:Interleukin-4