Increased levels of interleukin-6 are associated with lymphocytosis in bronchoalveolar lavage fluids of idiopathic nonspecific interstitial pneumonia

Local overexpression of interleukin-6 (IL-6) experimentally induces lymphocytic infiltration in the bronchial tree of rat. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia/fibrosis (NSIP) has an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid when compared with usual interstitial pneumonia (UIP). To reveal a relation of IL-6 with the lymphocyte infiltration of NSIP, IL-6 was measured in BAL fluids of idiopathic NSIP (n = 7), idiopathic UIP (n = 16), and normal control subjects (n = 45). IL-6-producing sites were assessed by IL-6 protein stain on biopsy specimens of NSIP, UIP, and normal lung of mediastinal tumors. Lymphocyte numbers and IL-6 levels in BAL fluids were higher in NSIP than those in UIP (p < 0.01, respectively), which were also higher when compared with those of normal control subjects (p < 0.01, respectively). In NSIP, the levels of IL-6 correlated with the number of lymphocytes (r = 0.93, p < 0.01). UIP cases were divided into two groups: high-UIP (n = 7) or low-UIP (n = 9) according to IL-6 levels greater than or within the 95 percentile of normal control subjects, respectively. The high-UIP group had BAL lymphocytosis when compared with the low-UIP group (p < 0.05). IL-6 stained on epithelial cells of the bronchial tree and on alveolar macrophages of NSIP and UIP. In conclusion, the lymphocytosis in BAL fluid of patients with NSIP and a subgroup of UIP is associated with the high levels of IL-6 and its sources are the epithelial cells of the small airway and the alveolar macrophages.