In a few patients with chronic sarcoidosis, prolonged, unacceptably high doses of corticosteroids are required to achieve symptomatic relief. In these cases, a corticosteroid-sparing drug might be administered to allow long-term treatment without the adverse effects of corticosteroids. This study examines azathioprine as a prednisolone-sparing treatment. In an open study, the course of 11 patients with chronic sarcoidosis was analysed. In an induction phase, 2 mg azathioprine x kg body weight (BW)(-1) x day(-1) in combination with 0.6-0.8 mg prednisolone x kg BW(-1) x day(-1) were administered with prednisolone being reduced to 0.1 mg x kg BW(-1) x day(-1) within 2-3 months. This was followed by a 21-22-month maintenance phase with 2 mg azathioprine x kg BW(-1) x day(-1) and 0.1 mg prednisolone x kg BW(-1) day(-1). Clinical parameters and immunological findings of bronchoalveolar lavage (BAL) were analysed. All patients had significant symptomatic relief and improvements or resolutions of physiological, serological and radiographic findings without suffering from serious adverse effects. Nine of 11 patients completed therapy after 19-26 months, and 2/11 patients terminated therapy after 8 and 12 months, respectively. Eight patients had remissions lasting 4-73 months. Three relapses occurred after 8, 18, and 22 months. During the induction phase, BAL cell composition changed and their activity in terms of cytokine release was suppressed. This preliminary study suggests that azathioprine may be effective as a corticosteroid-sparing agent in long-term therapy of sarcoidosis, but a much larger study is necessary to give the definitive answer.

SUMMARY An activation of T-cells that is

The evaluation of activation markers such as T4/T8 ratio and HLA-DR expression of lymphocytes of bronchoalveolar lavage (L-BAL) is an important clinical approach for the staging of sarcoidosis. However, it is not known to what extent this is paralleled by an exaggerated lymphocyte function. We investigated the dependence of L-BAL activation markers on the production of interleukin-2 (IL-2) by L-BAL and on the soluble IL-2 receptor serum level (sIL-2R) in 116 patients with sarcoidosis. In none of the combinations tested was a correlation between the two groups of parameters found; r less than 0.5, upper 90% confidence limit of r less than 0.8. Interestingly, IL-2 production is independent of HLA-DR+ T4 L-BAL, and sIL-2R production is independent of the percentage of IL-2+ L-BAL. Our data indicate that the L-BAL activation markers and the functional activity of T-cells represent independent phenomena.

In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1) by AM of 39 patients with chronic sarcoidosis (duration > 4 years; 30 active, 9 inactive diseases) without therapy and correlated the monokine release with parameters of T-cell alveolitis and the course of the disease. The T4/T8 ratio was higher in the active than in the inactive group without reaching statistical significance. TNFα as well as IL-1 is spontaneously released by AM of the active group 2,099 ± 518 pg/ml TNFα/10⁶ cells/24 h and 8/13 (IL-l+/total) respectively. In the inactive group the AM release 375 ± 246 pg/ml TNFα/106 cells/24 h which is in the range of the control and 1 out of 5 patients was IL-1-positive. There was no correlation between the monokine release and any parameter of T-cell alveolitis. These data support the hypothesis that the inflammatory process in chronic sarcoidosis is dominated by the activity of AM and that this activity determines the course of the disease.

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