Increased expression of IL-12 receptor mRNA in active pulmonary tuberculosis and sarcoidosis

Cytokines have been implicated in the pathophysiology and development of pu lmonary diseases such as tuberculosis and sarcoidosis. In particular, the n umbers of cells expressing Th1-type cytokines such as IFN-gamma and IL-12 a re increased within the lungs of patients with these granulomatous diseases . As a factor promoting the commitment of naive lymphocytes to a Th1-type p rofile of cytokine expression, IL-12 may be pivotal in the cascade of proin flammatory events within the airways. In this study, we examined the expres sion of the IL-12 receptor (IL-12R) mRNA in bronchoalveolar lavage (BAL) fl uid from patients with active pulmonary tuberculosis (n = 6) and active pul monary sarcoidosis (n = 6), and from allergic asthmatics (n = 6) and normal control subjects (n = 6). Bronchoscopy with BAL was undertaken, and cell c ytospins 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 co ntrast, the allergic asthmatic patients exhibited a significant decrease in the number of IL-12R mRNA-positive cells (both beta(1) and beta(2) subunit s (p < 0.01, p < 0.005, respectively), compared with the normal control sub jects. These patients did, however, exhibit a significant increase in IL-4R mRNA, which was not evident in those with either tuberculosis or sarcoidos is when compared with normal subjects (p < 0.05). Colocalization studies de monstrated 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 an d CD8+ve cells. The increased expression of receptors for IL-12 in granulom atous diseases such as pulmonary tuberculosis and sarcoidosis provides evid ence supporting the commitment of lymphocytes to a Th1-type cytokine profil e in vivo.