Spontaneous Release of Interleukin-2 by Lung T Lymphocytes in Active Pulmonary Sarcoidosis

We investigated the possible role of interleukin-2, a T-cell product that stimulates the clonal increase of responsive T lymphocytes, in the pathogenesis of pulmonary sarcoidosis. We obtained mononuclear effector cells from the lungs of 10 patients with sarcoidosis and high-intensity alveolitis, 17 patients with sarcoidosis and low-intensity alveolitis, 3 patients with idiopathic pulmonary fibrosis, and 10 normal controls. Lung cells from the group with sarcoidosis and low-intensity alveolitis, from the group with idiopathic pulmonary fibrosis, and from the controls produced insignificant amounts of interleukin-2. However, lung cells from 9 of 10 patients with sarcoidosis and high-intensity alveolitis spontaneously released interleukin-2, and in a proportion that correlated with the proportion of T cells in the lung washings (P<0.01). Blood T cells from the same patients did not release interleukin-2. To determine whether release of interleukin-2 by the lung T cells had a biologic effect in vivo, we measured T-lymphocyte replication in the lungs of patients and controls. The lung T lymphocytes replicated at a rate that was several times higher in the patients with sarcoidosis and high-intensity alveolitis than in the other patient groups or the controls (P<0.01). These observations suggest that the release of interleukin-2 by lung T cells has a central role in increasing the numbers of lung T cells in active pulmonary sarcoidosis. (N Engl J Med. 1983; 308:793–800.) Sarcoidosis is a chronic multisystem disorder characterized in affected organs by an accumulation of mononuclear inflammatory and immune effector cells, noncaseating granulomas, and derangement of normal tissue architecture.^1,2 Although most organs can be affected by this disorder, the lung is most commonly involved and is the site of disease that results in the highest morbidity and mortality.² The first manifestation of sarcoidosis in the lung is alveolitis, an accumulation of mononuclear effector cells within the alveolar structures.³ The alveolitis in active sarcoidosis is characterized by a marked increase in the number of activated T lymphocytes and, to a lesser degree,.