Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1119-1123

Increased Expression of IL-12 Receptor mRNA in Active Pulmonary Tuberculosis and Sarcoidosis

RAME A. TAHA, ELEANOR M. MINSHALL, RON OLIVENSTEIN, DAIZO IHAKU, BENOÎT WALLAERT, ANNE TSICOPOULOS, ANDRÉ-BERNARD TONNEL, ROBERTA DAMIA, DICK MENZIES, and QUTAYBA A. HAMID

Meakins-Christie Laboratories and Montreal Chest Research Institute, McGill University, Montreal, Quebec, Canada; and Pathologie Immuno-allergique Respiratoire et Cellules Inflammatoires, INSERM U416, Institut Pasteur de Lille, Cedex, France

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- 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 ₁ and 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 ₁ and 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.

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