title: Sulfasalazine and mesalamine modulate beryllium-specific lymphocyte proliferation and inflammatory cytokine production.
abstract: Occupational exposure to beryllium (Be) results in Be sensitization (BeS) that can progress to pulmonary granulomatous inflammation associated with chronic Be disease (CBD). Be-specific lymphocytes are present in the blood of patients with BeS and in the blood and lungs of patients with CBD. Sulfasalazine and its active metabolite, mesalamine, are clinically used to ameliorate chronic inflammation associated with inflammatory bowel disease. We tested whether sulfasalazine or mesalamine could decrease Be-stimulated peripheral blood mononuclear cell (PBMC) proliferation in subjects with CBD and BeS and Be-induced cytokine production in CBD bronchoalveolar lavage (BAL) cells. CBD (n = 25), BeS (n = 12) and healthy normal control (n = 6) subjects were enrolled and ex vivo proliferation and cytokine production were assessed in the presence of Be and sulfasalazine or mesalamine. Be-stimulated PBMC proliferation was inhibited by treatment with either sulfasalazine or mesalamine. Be-stimulated CBD BAL cell IFN-γ and TNF-α cytokine production was decreased by treatment with sulfasalazine or mesalamine. Our data suggest that both sulfasalazine and mesalamine interfere with Be-stimulated PBMC proliferation in CBD and BeS and dampens Be-stimulated CBD BAL cell proinflammatory cytokine production. These studies demonstrate that sulfasalazine and mesalamine can disrupt inflammatory pathways critical to the pathogenesis of chronic granulomatous inflammation in CBD, and may serve as novel therapy for human granulomatous lung diseases.
authors.affiliation: Department of Medicine, Robert H. Hollis Laboratory of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Dave R
authors.initials: DR
authors.lastname: Dobis
authors.forename: Richard T
authors.initials: RT
authors.lastname: Sawyer
authors.forename: May M
authors.initials: MM
authors.lastname: Gillespie
authors.forename: Lee S
authors.initials: LS
authors.lastname: Newman
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Day
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001607:Berylliosis / Q000276:immunology / Q000473:pathology; D001608:Beryllium / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D003710:Demography; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D008875:Middle Aged; D012460:Sulfasalazine / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D012460:Sulfasalazine; D019804:Mesalamine; D007371:Interferon-gamma; D001608:Beryllium