title: Increased expression of IL-12 receptor mRNA in active pulmonary tuberculosis and sarcoidosis.
abstract: Cytokines have been implicated in the pathophysiology and development of pulmonary diseases such as tuberculosis and sarcoidosis. In particular, the numbers of cells expressing Th1-type cytokines such as IFN-gamma and IL-12 are increased within the lungs of patients with these granulomatous diseases. As a factor promoting the commitment of naive lymphocytes to a Th1-type profile of cytokine expression, IL-12 may be pivotal in the cascade of proinflammatory events within the airways. In this study, we examined the expression of the IL-12 receptor (IL-12R) mRNA in bronchoalveolar lavage (BAL) fluid from patients with active pulmonary tuberculosis (n = 6) and active pulmonary sarcoidosis (n = 6), and from allergic asthmatics (n = 6) and normal control subjects (n = 6). Bronchoscopy with BAL was undertaken, and cell cytospins were examined using the technique of in situ hybridization. There was a significant increase in the numbers of cells expressing mRNA for both beta(1) and beta(2) subunits of the IL-12R in active pulmonary sarcoidosis (p < 0.02, p < 0.01, respectively) and active pulmonary tuberculosis (p < 0.01, p < 0.005, respectively) compared with normal control subjects. In contrast, the allergic asthmatic patients exhibited a significant decrease in the number of IL-12R mRNA-positive cells (both beta(1) and beta(2) subunits (p < 0.01, p < 0.005, respectively), compared with the normal control subjects. These patients did, however, exhibit a significant increase in IL-4R mRNA, which was not evident in those with either tuberculosis or sarcoidosis when compared with normal subjects (p < 0.05). Colocalization studies demonstrated that CD8+ve cells are a principal site for the expression of IL-12R in tuberculosis. In sarcoidosis, IL-12R was expressed both on CD4+ve and CD8+ve cells. The increased expression of receptors for IL-12 in granulomatous diseases such as pulmonary tuberculosis and sarcoidosis provides evidence supporting the commitment of lymphocytes to a Th1-type cytokine profile in vivo.
authors.affiliation: Meakins-Christie Laboratories and Montreal Chest Research Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Taha
authors.forename: E M
authors.initials: EM
authors.lastname: Minshall
authors.forename: R
authors.initials: R
authors.lastname: Olivenstein
authors.forename: D
authors.initials: D
authors.lastname: Ihaku
authors.forename: B
authors.initials: B
authors.lastname: Wallaert
authors.forename: A
authors.initials: A
authors.lastname: Tsicopoulos
authors.forename: A B
authors.initials: AB
authors.lastname: Tonnel
authors.forename: R
authors.initials: R
authors.lastname: Damia
authors.forename: D
authors.initials: D
authors.lastname: Menzies
authors.forename: Q A
authors.initials: QA
authors.lastname: Hamid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000150:complications / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D019948:Receptors, Interleukin-4