Shun Fujino

Evaluation of serum KL-6 levels in patients with pulmonary tuberculosis

SETTING KL-6, a human MUC-1 mucin preferentially expressed on type II pneumocytes, is a sensitive serum marker for evaluating alveolar damage of interstitial pneumonia and pulmonary fibrosis. Some patients with pulmonary tuberculosis develop severe respiratory dysfunction caused by extensive pulmonary fibrosis, compensatory emphysema and fibrous pleural thickening. OBJECTIVE To evaluate the clinico-pathological significance of KL-6 in pulmonary tuberculosis. DESIGN Serum KL-6 levels were measured in sera from 57 patients with active pulmonary tuberculosis and 38 healthy controls by a sandwich-type enzyme-linked immunosorbent assay. Immunohistochemistry was performed by an avidin-biotin-peroxidase complex method. RESULTS KL-6 levels were significantly higher in the patients than in the healthy controls (518 +/- 693 [SD] vs 227 +/- 91 U/ml, P < 0.001) and increased significantly according to the extent of pulmonary lesions evaluated by chest X-ray (P < 0.001). There was a significant negative correlation between serum KL-6 levels and % vital capacity (VC) (r = 0.642, P < 0.05). KL-6 was strongly expressed on proliferated type II pneumocytes and cuboidal epithelial cells adjacent to thickened intralobular septa and pleura. CONCLUSIONS In pulmonary tuberculosis, serum KL-6 originates from proliferated type II pneumocytes and cuboidal epithelial cells, and is a useful marker presenting the degree and extent of pulmonary fibroproductive lesions.

Evaluation of soluble IL-6 receptor concentration in serum and epithelial lining fluid from patients with interstitial lung diseases.

We measured soluble IL‐6 receptor (sIL‐6R) levels in serum and bronchoalveolar lavage fluids (BALF) from patients with interstitial pneumonia of unknown etiology (IP) (n= 17), sarcoidosis (n= 8) and normal control subjects (n= 10), to investigate its role in pulmonary diseases. Soluble IL‐6R was determined by an ELISA. The volume of epithelial lining fluid (ELF) in BALF was estimated using an urea method. We found that levels of sIL‐6R in serum, BALF, and ELF from patients with IP or sarcoidosis were significantly higher than those from normal subjects. Furthermore, levels of sIL‐6R in BALF or ELF were significantly correlated with those of albumin, indicating that sIL‐6R, together with albumin, may enter ELF as a result of the increased permeability caused by pulmonary inflammation. Thus most of the sIL‐6R in ELF would be from serum, and relatively small amounts of it might be produced locally. However, sIL‐6R levels in ELF, but neither serum nor BALF, were significantly correlated with levels of C‐reactive protein in patients with IP. These results suggest that both systemic and local production of sIL‐6R are increased, and raised sIL‐6R is involved in the modulation of systemic and local inflammatory responses in patients with IP and sarcoidosis.

Comparative studies of circulating KL-6, type III procollagen N-terminal peptide and type IV collagen 7S in patients with interstitial pneumonitis and alveolar pneumonia

KL-6, a MUC1 mucin preferentially expressed in regenerating type 2 pneumocytes, has been reported to be a sensitive serum marker for evaluating the disease activity of interstitial pneumonitis (IP). Type III procollagen N-terminal peptide (PIIIP) and type IV collagen 7S (7S collagen) have also been reported to be useful in the serological evaluation of the activity. Their levels were measured and their serodiagnostic values were compared simultaneously in patients with IP and alveolar pneumonia. The study population was 45 patients with IP and 12 patients with alveolar pneumonia. Serum KL-6 levels were measured by a specific enzyme immunoassay, and both serum PIIIP and 7S collagen concentrations by their correspondent radioimmunoassay kits. There were no significant difference of serum C-reactive protein level, which was evaluated as an indicator of inflammatory process, between IP and alveolar pneumonia patients. In IP, the abnormally elevated rate of KL-6 [80% (36/45)] was significantly higher than those of PIIIP [40% (18/45)] and 7S collagen [40% (18/45)]. In alveolar pneumonia, the rate of KL-6 [0% (0/12)] was significantly lower than those of PIIIP [33% (4/12)] and 7S collagen [25% (3/12)]. There were no significant correlations among serum levels of the markers. These observations indicate that the serodiagnostic value of KL-6 for IP is superior to that of PIIIP and 7S collagen, and that KL-6 has a characteristic to discriminate IP from alveolar pneumonia.

Soluble interleukin-6 receptor levels in pleural effusions

Generation of soluble cytokine receptors is a general phenomenon, and the roles of several such receptors have been investigated in clinical settings. Unlike other soluble cytokine receptors, soluble interleukin-6 receptor (sIL-6R) can act as an agonist and thus is implicated as an important modulator in the acute-phase reaction of prolonged inflammation. The purpose of the present study was to determine the roles of pleural sIL-6R in both differential diagnosis of pleural diseases and in the induction of acute-phase protein. Specific sandwich enzyme-linked immunosorbent assays were used to determine sIL-6R and IL-6 in 19 tuberculous, 48 malignant and 10 transudative effusions. Although IL-6 levels in pleural effusions were strikingly different, no significant differences in pleural sIL-6R levels were found between the groups. Pleural levels of IL-6 were invariably much higher, whereas those of SIL-6R were invariably lower than serum levels. Furthermore, IL-6, but not sIL-6R, levels in effusions correlated significantly with serum C-reactive protein levels. These results suggest that: (1) pleural levels of sIL-6R are not increased even in strong inflammation such as tuberculous pleurisy, nor significantly different among pleural diseases; and (2) the local levels of sIL-6R are not as important as expected for the induction of acute-phase proteins in patients with pleural diseases.