In a recent phase I study of inhalative, human natural interleukin-2 (hnIL-2) treatment of pulmonary metastases from previously resected solid tumors (mainly renal carcinoma), we have reported that this treatment resulted in an increased accessory function of alveolar macrophages (AM) [1]. Encouraged by these data, we investigated the influence of hnIL-2 inhalation on proinflammatory cytokines spontaneously released by AM. Bronchoalveolar lavage was performed in four groups, each of four patients, before and after 2 weeks of daily inhalation of 0, 200,000, 600,000 and 1,200,000 IU of hnIL-2, respectively. Bronchoalveolar cells were cultured without stimulation to allow spontaneous release over a period of 24 h, into the supernatant. Concentrations of tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) were determined by the ELISA technique. Before hnIL-2 inhalation, we measured the following spontaneous cytokine release: TNF-alpha: 1,115.4 +/- 469.1 pg/ml, IL-6: 267.5 +/- 67.7 pg/ml cells, IL-8: 137.8 +/- 40.5 ng/ml, MIP-1alpha: 9.5 +/- 6.8 ng/ml. Inhalation of hnIL-2 did not result in any significant changes in these cytokines. Comparing TNF-alpha release in healthy controls (250.6 +/- 46.7 pg/ml) with that of tumor patients (1,115.4 +/- 469.1 pg/ml), we observed significantly (p < 0.05) elevated TNF-alpha levels in the patient group, which did not change significantly in response to IL-2 inhalation. Our data demonstrate that the activation of AM previously observed after hnIL-2 inhalation is not directly related to a hnIL-2-induced cytokine release by bronchoalveolar cells.