Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis

David R. Moller*, Jeffrey D. Forman, Mark C. Liu, Paul W. Noble, Brian M. Greenlee, Prachi Vyas, David A. Holden, Joseph M. Forrester, Angeline Lazarus, Maria Wysocka, Giorgio Trinchieri, Christopher Karp

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

338 Scopus citations


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 I cytokine expression, with elevated mRNA and protein levels of IFN-γ, 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.

Original languageEnglish
Pages (from-to)4952-4960
Number of pages9
JournalJournal of Immunology
Issue number12
StatePublished - 15 Jun 1996
Externally publishedYes


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