Increased expression of CCL4/MIP-1ß in CD8+ cells and CD4+ cells in sarcoidosis.

Sarcoidosis is a granulomatous disease with an increased accumulation of T cells in lungs as a result of on-site proliferation and chemotaxis induced by chemokines. It has already been demonstrated that CCL3-5 levels were increased in BAL fluid of sarcoidosis patients. To analyze the expression of CCL3-5 chemokines by T-cell subtypes (CD4+, CD8+, Th1, Th2, Tc1 or Tc2) in the lungs of sarcoidosis patients, fifteen untreated sarcoidosis patients and eighteen control subjects were enrolled in this study. CD4+ and CD8+ cells were isolated from BAL fluid by positive magnetic selection. The expression of CCL3-5 and other cytokines in CD4+ and CD8+ cells were measured by flow cytometry. The percentage of CD4+ or CD8+ cells expressing CCL4 were significantly higher in sarcoidosis patients (22.3% and 58.1%) compared to those seen in healthy subjects (11.1% and 16.5%, P = 0.04 and P = 0.02, respectively). In addition, the expression of CCL3, CCL4 and CCL5 was significantly elevated in CD8+ cells (8.9%, 58.1% and 2.1%) compared to CD4+ cells (2.1%, 22.3% and 0.7%; P = 0.04, P = 0.009 and P = 0.04, respectively), whereas CCL4 was expressed by significantly more Tc1 than Th1 cells in sarcoidosis patients (P = 0.006). Our study shows the possible role of CD8+ cells and CD4+ cells in recruiting T cells to the site of inflammation in sarcoidosis through the release of CCL4, either alone or together with Th1/Tc1-associated cytokines.

Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine.

BACKGROUND: Interleukin-17 (IL-17) is a novel cytokine secreted by activated human memory CD4+ T cells. In vivo IL-17 recruits neutrophils into the airways via the release of CXC chemokines (interleukin-8) from bronchial epithelial cells. Since neutrophils are implicated in pathogenesis of chronic obstructive pulmonary disease (COPD) chronic bronchitis (CB) and asthma, we hypothesized that there would be increased concentration of IL-17 in the airways of these patients. To test this hypothesis, we measured levels of IL-17 in induced sputum of COPD patients, chronic bronchitis and asthmatics and compared them with healthy controls. METHODS: Levels of IL-17 in induced sputum were measured via ELISA method in 19 COPD, 16 CB, 10 asthma and 11 control subjects. Airway responsiveness to methacholine was performed in people with FEV1 higher than 70% of predicted. RESULTS: There were no significant differences in IL-17 levels between control group and the other groups. However, levels of IL-17 in sputum of COPD patients were significantly lower than in asthma (P=0.004) and in CB (P=0.01) groups. Medians and (ranges) were as follows: asthma--37.6 pg/ml (18.8-55.7 pg/ml), CB 293 pg/ml (18.8-49.7 pg/ml) and COPD 24.6 pg/ml (0-34.1 pg/ml). Comparison of healthy control subjects (PC20 > 8 mg/ml) to a group with bronchial hyperreactivity, which consisted of asthmatics and CB patients, whose PC20 was less than 8 mg/ml, revealed that levels of IL-17 were significantly increased in the second group (P=0.02). Also, levels of IL-17 were significantly increased (P=0.02) in the asthmatic patients with bronchial hyperreactivity compared to healthy subjects. Moreover levels of IL-17 in sputum of all studied subjects correlated negatively with PC20 (r=-0.51, P=0.002). CONCLUSIONS: According to our results IL-17 is probably not involved in pathogenesis of stable COPD, but it may play a role in people with airway hyperresponsiveness.

[Levels of CC-chemokine (MCP-1 alpha, MIP-1 beta) in induced sputum of patients with chronic obstructive pulmonary disease and patients with chronic bronchitis]. / Stezenia CC-chemokin (MCP-1, MIP-1 alpha, MIP-1 beta) w indukowanej plwocinie u chorych na przewlekla obturacyjna chorobé pluc i u chorych na przewlekle zapalenie oskrzeli.

BACKGROUND: MCP-1, MIP-1 alpha and MIP-1 beta are CC-chemokines, which act as chemoattractants for inflammatory cells like macrophages, lymphocytes and eosinophils. These cells are known to be important for development of chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB). METHODS: Sputum was obtained from 14 patients with COPD, 12 patients with CB and 14 healthy persons by means of the sputum induction method. The MCP-1, MIP-1 alpha and MIP-1 beta levels were measured in induced sputum via ELISA method. RESULTS: MIP-1 alpha levels in sputum were significantly higher in CB patients compared to healthy persons (p = 0.01). Median and (range) were following: CB patients--22.7 pg/ml (9.2-95.9 pg/ml), control subjects--17.5 pg/ml (0-27.1 pg/ml). The MIP-1 beta levels in sputum were significantly higher in COPD patients compared to healthy persons (p = = 0.003). Median and (range) were following: COPD patients--173.2 pg/ml (30.6-1880 pg/ml), control subjects--19.0 pg/ml (0-570.5 pg/ml). No significant differences were detected among studied groups for MCP-1 levels in induced sputum. There was positive correlation in CB group between levels of MIP-1 beta and number of eosinophils in gram of sputum (r = 0.81 and p = 0.001). CONCLUSIONS: MIP-1 alpha maybe important for development of chronic bronchitis and MIP-1 beta for development of chronic obstructive pulmonary disease. MIP-1 beta is probably a chemoattractant for eosinophils in patients with chronic bronchitis.

[Remarks about good clinical practice]. / Uwagi na temat zasad prawidlowego prowadzenia badan klinicznych.

In September 1998 Polish translation of the newest Good Clinical Practice version was issued by Polish Department of Health and Social Care. It is essential for all investigators who carry out the clinical researches involving human subjects to become acquainted with the Good Clinical Practice principles.