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Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis.
J Immunol. 1996 Jun 15; 156(12):4952-60.JI

Abstract

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by the expansion of activated oligoclonal CD4+ T cells and macrophages at sites of disease. To investigate the immunopathogenesis of sarcoidosis, we analyzed patterns of cytokine expression in bronchoalveolar lavage cells and fluid from patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis and from normal volunteers. We found dominant type 1 cytokine expression, with elevated mRNA and protein levels of IFN-gamma, but not IL-4, in sarcoid lung cells and fluid compared with those in normal samples. To define immunoregulatory mechanisms important to this type 1 response, we analyzed the expression of IL-12 and IL-10 in lung cells and fluid. Using semiquantitative PCR, we found significantly higher mRNA expression of the regulated IL-12 p40 subunit, but not IL-10, in sarcoid compared with normal lung cells. Consistent with these observations, strikingly elevated levels of p40 protein were found in sarcoid compared with normal bronchoalveolar lavage fluid. Unstimulated and Staphylococcus aureus-stimulated sarcoid alveolar macrophages produced greater amounts of IL-12 than normal alveolar macrophages when cultured in vitro. We hypothesize that sarcoidosis is a Th1-mediated disease driven by chronic, dysregulated production of IL-12 at sites of disease.

Authors+Show Affiliations

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8648147

Citation

Moller, D R., et al. "Enhanced Expression of IL-12 Associated With Th1 Cytokine Profiles in Active Pulmonary Sarcoidosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 156, no. 12, 1996, pp. 4952-60.
Moller DR, Forman JD, Liu MC, et al. Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis. J Immunol. 1996;156(12):4952-60.
Moller, D. R., Forman, J. D., Liu, M. C., Noble, P. W., Greenlee, B. M., Vyas, P., Holden, D. A., Forrester, J. M., Lazarus, A., Wysocka, M., Trinchieri, G., & Karp, C. (1996). Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis. Journal of Immunology (Baltimore, Md. : 1950), 156(12), 4952-60.
Moller DR, et al. Enhanced Expression of IL-12 Associated With Th1 Cytokine Profiles in Active Pulmonary Sarcoidosis. J Immunol. 1996 Jun 15;156(12):4952-60. PubMed PMID: 8648147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis. AU - Moller,D R, AU - Forman,J D, AU - Liu,M C, AU - Noble,P W, AU - Greenlee,B M, AU - Vyas,P, AU - Holden,D A, AU - Forrester,J M, AU - Lazarus,A, AU - Wysocka,M, AU - Trinchieri,G, AU - Karp,C, PY - 1996/6/15/pubmed PY - 1996/6/15/medline PY - 1996/6/15/entrez SP - 4952 EP - 60 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 156 IS - 12 N2 - Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by the expansion of activated oligoclonal CD4+ T cells and macrophages at sites of disease. To investigate the immunopathogenesis of sarcoidosis, we analyzed patterns of cytokine expression in bronchoalveolar lavage cells and fluid from patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis and from normal volunteers. We found dominant type 1 cytokine expression, with elevated mRNA and protein levels of IFN-gamma, but not IL-4, in sarcoid lung cells and fluid compared with those in normal samples. To define immunoregulatory mechanisms important to this type 1 response, we analyzed the expression of IL-12 and IL-10 in lung cells and fluid. Using semiquantitative PCR, we found significantly higher mRNA expression of the regulated IL-12 p40 subunit, but not IL-10, in sarcoid compared with normal lung cells. Consistent with these observations, strikingly elevated levels of p40 protein were found in sarcoid compared with normal bronchoalveolar lavage fluid. Unstimulated and Staphylococcus aureus-stimulated sarcoid alveolar macrophages produced greater amounts of IL-12 than normal alveolar macrophages when cultured in vitro. We hypothesize that sarcoidosis is a Th1-mediated disease driven by chronic, dysregulated production of IL-12 at sites of disease. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8648147/Enhanced_expression_of_IL_12_associated_with_Th1_cytokine_profiles_in_active_pulmonary_sarcoidosis_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=8648147 DB - PRIME DP - Unbound Medicine ER -