interleukin-8 and Sarcoidosis--Pulmonary

Angiogenesis is an important process involved in the pathogenesis of diffuse parenchymal lung diseases. The aim of the study was to compare the angiogenic profile of patients with sarcoidosis and idiopathic pulmonary fibrosis (IPF) based on analysis of circulating factors.. Serum concentrations of angiopoietin-2 (Ang-2), follistatin, granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-8 (IL-8), platelet derived growth factor-BB (PDGF-BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1) and vascular endothelial growth factors (VEGF) were measured in the patients and the healthy subjects.. Serum concentrations of G-CSF, follistatin, PECAM-1 and IL-8 were significantly higher in the IPF patients in comparison with the control group and the sarcoid patients. PDGF-BB concentrations were also significantly higher in serum of IPF patients than in sarcoid patients, but not than in the controls. In contrast, Ang-2 and VEGF concentrations did not differ significantly between the three groups. In the sarcoid patients, irrespective of the disease activity or the radiological stage, serum concentrations of these cytokines were similar to the control group.. These results indicate that differences may exist in angiogenic activity between patients with parenchymal lung diseases. In contrast to sarcoidosis, IPF is characterized by a higher serum concentration of different molecules involved in the angiogenic processes .

Topics: Adult; Becaplermin; Biomarkers; Case-Control Studies; Female; Follistatin; Forced Expiratory Volume; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Male; Middle Aged; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Proteins c-sis; Sarcoidosis; Sarcoidosis, Pulmonary; Vascular Endothelial Growth Factor A; Vesicular Transport Proteins; Vital Capacity

Angiogenesis-angiostasis balance and leukocyte recruitment are influenced by different concentrations of distinct chemokines.. To investigate the relative contribution of angiogenic and angiostatic CXC chemokines to the pathogenesis of idiopathic pulmonary fibrosis (IPF) and granulomatous lung diseases, we examined the in vitro production of an angiogenic chemokine (IL-8), and 2 angiostatic chemokines (IP-10 and MIG) by alveolar macrophages.. Alveolar macrophages from 16 patients with granulomatous lung diseases [8 with sarcoidosis, 8 with extrinsic allergic alveolitis (EAA)], 16 patients with IPF, and 8 control subjects were cultured for 24 h. IL-8, IL-18, IP-10 and MIG in the culture supernatants were measured by a fluorescent bead-based multiplex technique.. In IPF patients, IL-8 was increased and correlated with bronchoalveolar lavage (BAL) neutrophils, whereas the levels of IP-10 and MIG were normal. In sarcoidosis and EAA patients, IL-8, IP-10, and MIG were all increased and IP-10 and MIG correlated with IL-18, a Th1 cytokine, and the percentage and number of BAL lymphocytes.. The difference in the expression of CXC chemokines and a Th1 cytokine may contribute to the different immunopathogenesis, clinical course and responsiveness to treatment of these diseases.

Topics: Aged; Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Case-Control Studies; Cells, Cultured; Chemokine CXCL10; Chemokine CXCL9; Eosinophils; Female; Humans; Interleukin-18; Interleukin-8; Male; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary

Activated macrophages have been characterized as M1 and M2 according to their inflammatory response pattern. Here we analyzed the M2 marker expression and intracellular signal transduction in the course of cytokine-driven differentiation. We found elevated spontaneous production of the chemokines CCL17, CCL18 and CCL22 and increased expression of CD206 by alveolar macrophages from patients with lung fibrosis. Stimulation of normal human AM with Th2 cytokines IL-4 and/or IL-10 in vitro revealed IL-4 as the most powerful inducer of M2-phenotype in AM and monocytes. Importantly, IL-10 enhanced IL-4-induced expression of CCL18 and IL-1RA in a synergistic fashion. IL-4/IL-10 stimulation induces a strong activation of STAT3 in AM from fibrosis patients. These results suggest an important role for M2 polarized AM in the pathogenesis of pulmonary fibrosis and indicate that both IL-4 and IL-10 account for human AM phenotype shift to M2, as seen in patients with fibrotic interstitial lung diseases.

Topics: Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Chemokines, CC; Cytokines; Female; Gene Expression; Humans; Idiopathic Pulmonary Fibrosis; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-4; Interleukin-8; Lectins, C-Type; Macrophage Activation; Macrophages, Alveolar; Male; Mannose Receptor; Mannose-Binding Lectins; Middle Aged; Monocytes; Pulmonary Fibrosis; Receptors, Cell Surface; Sarcoidosis, Pulmonary; Scleroderma, Systemic; Signal Transduction; STAT Transcription Factors; Tumor Necrosis Factor-alpha; Young Adult

Sarcoidosis is a disease of unknown etiology. Little is known of predictive factors of fibrosis. It was suggested that PAI-1, uPA, TGF-beta1, VEGF, IL-8, TNF-alpha influence this process.. To assess airway inflammatory and fibrosis markers in EBC in sarcoidosis and the effect of fiberoptic bronchoscopy (FOB), bronchoalveolar lavage fluid (BALF), transbronchial lung biopsy (TBLB) and bronchial mucosa membrane biopsy on their production in the airways.. The study group consisted of 11 patients (5 women, 6 men; mean age 40 +/- 9 yrs, mean +/- SD) with sarcoidosis stage I-III. PAI-1 (ng/ml), uPA (ng/ml), TGF-beta1 (pg/ml), VEGF (pg/ml), IL-8 (pg/ml), TNF-alpha (pg/ml) levels were measured in BALF and EBC collected before and 48 hours after FOB.. No significant changes in EBC levels of VEGF, PAI-1, TGF-beta1, TNF-alpha (respectively: 8.02 +/- 4.97 pg/ml; 1.1 +/- 1.2 ng/ml; 2909.7 +/- 206.6 pg/ml; 10.7 +/- 19.9 pg/ml) after FOB were observed when compared to baseline. In contrast, IL-8 concentration in EBC (pg/ml) decreased after FOB (0.073 +/- 0.13 v. 0.061 +/- 0.1, p = 0.006) and was significantly lower than in BALF (BALF 0.95 +/- 0.62, p < 0.05). Also, mean level of VEGF was higher in BALF than in EBC both pre- and post- FOB (BALF 66.38 +/- 36.95, EBC pre-FOB 6.75 +/- 3.67 and EBC post-FOB 8.02 +/- 4.97). Significant relationship between TNF-alpha in post-FOB EBC and BALF was also shown (b = 0.63, p = 0.04).. FOB does not significantly affect levels of airway inflammation and fibrosis markers present in EBC before and after FOB; they were also comparable to the concentrations marked by BALF. The lack of correlation between markers levels in EBC and BALF indicates that these methods are not equivalent. Due to repeatibility, and less invasive, simple method of EBC test it seems reasonable to continue the research on the larger number of patients.

Topics: Adult; Biomarkers; Breath Tests; Bronchoalveolar Lavage Fluid; Cytokines; Female; Humans; Interleukin-8; Male; Middle Aged; Pilot Projects; Plasminogen Activator Inhibitor 1; Sarcoidosis, Pulmonary; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Sarcoidosis is a systemic disease of unknown aetiology characterised by granuloma formation and the presence of interferon γ (IFNγ)-producing T cells that cause inflammation and tissue damage in multiple organs, especially the lung. Exosomes are nano-sized immunomodulatory vesicles of endosomal origin released from a diverse range of cells and are also found in physiological fluids including bronchoalveolar lavage fluid (BALF) from healthy individuals.. To investigate whether exosomes are enriched in the lungs of patients with sarcoidosis compared with healthy individuals and whether they could contribute to pathogenesis.. BALF exosomes from patients with sarcoidosis (n=36) and healthy controls (n=14) were compared by electron microscopy, flow cytometry, western blot analysis and mass spectrometry. BALF exosomes were incubated with autologous peripheral blood mononuclear cells (PBMCs) or the human bronchial epithelial cell line 16HBE14o-. Cytokines were measured by ELISPOT and ELISA.. BALF from patients with sarcoidosis showed increased levels of exosomes compared with healthy individuals. Exosomes from patients showed significantly higher expression of MHC class I and II, tetraspanins CD9, CD63 and CD81 as well as neuregulin-1, known to be associated with cancer progression. Furthermore, BALF exosomes from patients induced significantly higher IFNγ and interleukin (IL)-13 production in autologous PBMCs compared with healthy individuals and could also stimulate IL-8 production from epithelial cells.. The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.

Topics: Adult; Bronchoalveolar Lavage Fluid; Cell Line; Cells, Cultured; Cytokines; Epithelial Cells; Exosomes; Female; Humans; Inflammation Mediators; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Proteins; Sarcoidosis, Pulmonary; Young Adult

Sarcoidosis is a systemic granulomatous disorder of unknown aetiology involving multiple organs and often associated with non-granulomatous microangiopathic lesions in various organs. Increased angiogenesis-inducing ability of activated alveolar macrophages was found in bronchoalveolar specimens from patients with pulmonary sarcoidosis and from patients with extrapulmonary involvement. In contrast, decreased levels of vascular endothelial growth factor (VEGF) were found in BAL fluid recovered from sarcoid-associated pulmonary fibrosis. This study evaluated whether sarcoidosis is associated with abnormalities of VEGF and IL-8 in induced sputum (IS) samples.. Twenty-three sarcoid patients and 13 controls performed IS. CD4/CD8 T-cell subsets were measured, as were pulmonary function tests and VEGF and IL-8.. Sarcoid patients showed significantly higher mean %lymphocytes (P = 0.04), significantly higher mean CD4/CD8 ratio (P = 0.0001) and significantly lower VEGF levels (P = 0.03) than controls. Patients with stages III-IV sarcoidosis showed a lower level of VEGF compared with those with stages I-II sarcoidosis (P = 0.048). IL-8 was detected in 10/35 samples and positively correlated with % neutrophils (P = 0.054) and eosinophils (P = 0.045). VEGF immunohistochemical staining showed a mixed pattern of expression in the same tissue samples and was low in fibrotic tissue areas.. VEGF in IS samples may reflect impairment in angiogenesis associated with the extent of sarcoid fibrosis and functional disorders.

Topics: Adult; Case-Control Studies; CD4-CD8 Ratio; Female; Humans; Immunohistochemistry; Interleukin-8; Lymphocyte Subsets; Male; Middle Aged; Neovascularization, Pathologic; Sarcoidosis, Pulmonary; Sputum; Vascular Endothelial Growth Factor A

Recent evidence has shown that several chemokines--including those involved in angiogenesis--have been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and sarcoidosis. We speculated that these differences could be attributed to distinct angiogenic and angiostatic profiles. This hypothesis was investigated by estimating the levels of three angiogenic chemokines (growth-related gene [GRO]-alpha, epithelial neutrophil-activating protein [ENA]-78, and interleukin [IL]-8), and three angiostatic chemokines (monokine induced by interferon (IFN)-gamma [MIG], IFN-gamma-inducible protein [IP]-10, and IFN-gamma-inducible T-cell alpha chemoattractant) in serum and BAL fluid (BALF).. We studied prospectively 20 patients with sarcoidosis (median age, 46 years; range, 25 to 65 years), 20 patients with IPF (median age, 68 years; range, 40 to 75 years), and 10 normal subjects (median age, 39 years; range, 26 to 60 years).. The GRO-a serum and BALF levels of IPF patients were found significantly increased in comparison with healthy subjects (799 pg/mL vs 294 pg/mL [p = 0.022] and 1,827 pg/mL vs 94 pg/mL [p < 0.001], respectively) and sarcoidosis patients (799 pg/mL vs 44 pg/mL [p < 0.001] and 1,827 pg/mL vs 214 pg/mL [p < 0.001], respectively). Moreover, ENA-78 and IL-8 BALF levels in IPF patients were significantly higher compared with sarcoidosis patients (191 pg/mL vs 30 pg/mL [p < 0.001] and 640 pg/mL vs 94 pg/mL [p = 0.03], respectively). MIG serum levels in IPF patients were found significantly upregulated in comparison with sarcoidosis patients and healthy control subjects. However, MIG and IP-10 BALF levels (1,136 pg/mL vs 66 pg/mL [p < 0.001] and 112 pg/mL vs 56 pg/mL [p = 0.037], respectively) were significantly higher in sarcoidosis patients compared with IPF patients.. Our data suggest distinct angiogenic profiles between IPF and sarcoidosis, indicating a potential different role of CXC chemokines in the local immunologic response in IPF and pulmonary sarcoidosis.

Topics: Adult; Aged; Angiostatic Proteins; Bronchoalveolar Lavage Fluid; Chemokine CXCL1; Chemokine CXCL10; Chemokine CXCL5; Chemokine CXCL9; Chemokines; Chemokines, CXC; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Lung; Male; Middle Aged; Pulmonary Fibrosis; Reference Values; Sarcoidosis, Pulmonary

In comparison with neutrophil-mediated lung diseases, such as acute respiratory distress syndrome, the involvement of IL-8 in lymphocyte-mediated lung diseases has not been fully investigated. Several reports have shown a slight increase in bronchoalveolar lavage fluid (BALF) IL-8 in patients with hypersensitivity pneumonitis (HP) and sarcoidosis (SAR), but the source of the IL-8 has not been clarified. In the present study, the in vivo production of IL-8 by alveolar macrophages (AMs) is examined in these patients by analyzing the cell-associated IL-8, using the flow cytometric method adopted previously. The IL-8 levels in the epithelial lining fluid (ELF) were also assessed. Initially, slight, but significant, increased levels of ELF IL-8 in HP and SAR were confirmed. Using flow cytometric analysis, a significant increase was found in the cell-associated IL-8 of the freshly isolated AMs in HP, but not in SAR, indicating in vivo production of IL-8 by AMs in HP. The cell-associated IL-8 of the AMs cultured with or without lipopolysaccharide was also analyzed. However, in contrast to previous findings in patients with idiopathic pulmonary fibrosis, no differences were found between SAR and HP patients and control subjects. Based on these findings, it is speculated that ELF IL-8 levels are slightly increased in HP and SAR, and they may contribute to the accumulation of neutrophils and possibly lymphocytes. However, the source of IL-8 may be different and AMs are the candidate source of IL-8 in HP, but not in SAR. The flow cytometric method may be useful in assessing cytokines production by AMs.

Topics: Adult; Alveolitis, Extrinsic Allergic; Blood Urea Nitrogen; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cell Count; Cells, Cultured; Flow Cytometry; Humans; Interleukin-8; Lipopolysaccharides; Lymphocytes; Macrophages, Alveolar; Middle Aged; Neutrophils; Respiratory Mucosa; Sarcoidosis, Pulmonary; Serum Albumin

To evaluate the role of cytokines released by the inflammatory cells and immunocytes from patients in pathogenesis of developing sarcoidosis.. With well- microchemotaxis and allergy immunology, the level of tumor necrosis factor-alpha (TNF-alpha) and neutrophil chemotactic factor (NCF) was measured in the serum and BALF of 11 sarcoidosis and 7 IPF and 8 normal subjects (non-smokers).. The levels of TNFalpha (11.9 +/- 3.2, 11.7 +/- 3.0 ng x L(-1)) and NCF (191 +/- 51, 203 +/- 44 cell x 10HP(-1)) of BALF in the patients with sarcoidosis and IPF were significantly higher than these in control group (P < 0.01) and were higher than those in serum. The level of TNF-alpha in the BALF of patients with sarcoidosis was positively correlated with the percentage of lymphocytes (r = 0.73, P < 0.01). The activity of NCF in the BALF of patients with IPF was positively correlated with the percentage of neutrophils (r = 0.89, P < 0.01).. It indicated that TNF-alpha and NCF might play an important role in the pathogenetic process of the sarcoidosis and IPF, and can act as the marker of activity of these diseases.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Female; Humans; Interleukin-8; Male; Middle Aged; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Tumor Necrosis Factor-alpha

To investigate the relationship between the level of the neutrophil chemotactic factor(NCF), tumor necrosis factor-alpha(TNF-alpha) in patients with interstitial lung disease(ILD) and the activity of ILD.. The NCF activities in the BALF and in the serum from 11 patients with sarcoidosis, 7 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects were determined using the membrane filter and radio-immunoassay. The level of TNF-alpha was also detected.. In the 7 IPF patients, the level of NCF and TNF-alpha (203 +/- 44 cells/10 HP, 11.7 +/- 2.9 ng/L) in the BALF was higher than that in 8 control patients (83 +/- 45 cells/10 HP, 6.5 +/- 1.4 ng/L, P < 0.01). The level of NCF and TNF-alpha in the BALF from 11 patients with sarcoidosis (186 +/- 50 cells/10 HP, 12 +/- 3 ng/L) was highet than those in 8 control patients (P < 0.01). The level of NCF and TNF-alpha in the BALF from patients with IPF was positive correlated with the percentage of neutrophil (NCF: r = 0.89, P < 0.01; TNF-alpha: r = 0.86, P < 0.05). The level of NCF and TNF-alpha in the BALF of patients with sarcoidosis was positive correlated with the percentage of lymphocyte (NCF: r = 0.78, P < 0.01; TNF-alpha: r = 0.73, P < 0.01.. The level of NCF and TNF-alpha in the BALF from patients with IPF and sarcoidosis can act as the marker of the activity of alveolitis of IPF and sarcoidosis.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Female; Humans; Interleukin-8; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Tumor Necrosis Factor-alpha

We measured the levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the bronchoalveolar lavage (BAL) fluids from 27 patients with active pulmonary sarcoidosis and examined the relationship between chemokine levels and some clinical manifestations. The levels of two chemokines were assessed by enzyme-linked immunosorbent assay. There were significant positive correlations between the absolute number of lymphocytes and MCP-1 levels. The level of MCP-1 was significantly higher in the group with age at onset of over 50 year than that in the group with age at onset under 30 year. There were no significant differences between the non-smokers and smokers, or among the groups of patients classed according to stages. We conclude that MCP-1 can play an important role in the pathogenesis and clinical course of pulmonary sarcoidosis, although further analysis is needed to delineate the exact role of IL-8.

Topics: Adolescent; Adult; Age of Onset; Animals; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Enzyme-Linked Immunosorbent Assay; Female; Guinea Pigs; Humans; Interleukin-8; Lymphocytes; Macrophages; Male; Middle Aged; Sarcoidosis, Pulmonary; Smoking

We evaluated the contribution of interleukin-8 (IL-8) to the pathogenesis of idiopathic pulmonary fibrosis (IPF) by studying bronchoalveolar lavage fluid (BALF) in eight patients with IPF in the chronically progressive phase, five patients with IPF in the subacutely progressive phase, eight patients with sarcoidosis (SAR), and eight control (CTL) subjects. IL-8 levels were not increased in the BALF of the patients with IPF in the chronic phase (11.3 +/- 8.8 pg/ml), nor in that of the SAR patients (13.8 +/- 7.8 pg/ml), whereas they were increased in the BALF of patients with IPF in the subacutely progressive phase (1.93 +/- 1.10 ng/ml). We then investigated extracellular and cell-associated IL-8 in lipopolysaccharide (LPS)-stimulated BALF cells to determine the IL-8-producing potential of alveolar macrophages (AM). Following LPS stimulation of BALF cells from patients with IPF in the chronic phase, both the extracellular IL-8 in culture fluid and the cell-associated IL-8 in AM were increased as compared with those for the CTL subjects (p < 0.05 and p < 0.05, respectively). These results suggest that AM of patients with IPF are primed for IL-8 production. We conclude that IL-8 may play a role in neutrophilic alveolitis, especially during the subacute phase of IPF.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Analysis of Variance; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Chronic Disease; Escherichia coli; Female; Humans; Interleukin-8; Lipopolysaccharides; Macrophage Activation; Macrophages, Alveolar; Male; Middle Aged; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Stimulation, Chemical

Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease caused by the inhalation of a variety of antigens and is characterized by a dramatic accumulation of inflammatory cells, including neutrophils, lymphocytes and macrophages, in the lung. The mechanisms implicated in the inflammatory cell recruitment observed in hypersensitivity pneumonitis are unknown. We examined the concentrations of two important chemokines, interleukin-8 (IL-8) and monocyte chemoattractant protein-1/monocyte chemotactic and activating factor (MCP-1/MCAF), in the bronchoalveolar lavage fluid (BALF) of patients with summer-type hypersensitivity pneumonitis (n = 8), and compared them with those in patients with sarcoidosis (n = 13) and with controls (n = 8). In the BALF of summer-type hypersensitivity pneumonitis, the levels both of IL-8 and MCP-1 were significantly increased compared with levels measured in control subjects. On the other hand, compared to the control value, the MCP-1 level in the BALF of the sarcoidosis patients was significantly increased, but IL-8 was only slightly and nonsignificantly increased. Since IL-8 is a chemoattractant for neutrophils and T-lymphocytes, whereas MCP-1 acts mainly on monocytes/macrophages, our findings may indicate that these two chemokines participate in the cellular accumulation observed in hypersensitivity pneumonitis.

Topics: Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Case-Control Studies; Chemokine CCL2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Sarcoidosis, Pulmonary; Seasons

Numerous cytokines are thought to be important in the pathogenesis of granulomatous inflammation and subsequent fibrosis in sarcoidosis. Interleukin (IL)-6 and IL-8, two recently described cytokines with a broad spectrum of proinflammatory effects, could participate in this disease. We obtained bronchoalveolar lavage fluid (BALF) from 16 subjects (13 African-American, three Caucasian) with untreated active pulmonary sarcoidosis and 10 healthy nonsmoking volunteers (nine Caucasian, one African-American). Concentrated BALF was analyzed by an ELISA for IL-6, IL-8, and albumin. The median IL-6 level was 9.8 pg/mg albumin (range, 0-278) for the sarcoid group compared with 0.14 pg/mg (range, 0.14-9.8) in the control subjects (p = 0.001). The corresponding values for IL-8 were 202 pg/mg (range, 35-2179) versus 5.0 pg/mg (range, 0-44) in the control subjects (p < 0.001). Among the sarcoid patients, BALF IL-6 and IL-8 levels correlated with each other (r = 0.96, p < 0.001), and both cytokines correlated with the BALF neutrophil percentage (r = 0.96 and 0.95, respectively; p < 0.001 for both). No difference was detected in IL-8 concentrations as measured by ELISA in culture supernatants of alveolar macrophages obtained from five sarcoid patients and five control subjects. We conclude that IL-6 and IL-8 are elevated in BALF of patients with active sarcoidosis and may be important modulators of the disease process.

Topics: Adult; Albumins; Bronchoalveolar Lavage Fluid; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Macrophages, Alveolar; Male; Sarcoidosis, Pulmonary

The potential for interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) to induce neutrophil and mononuclear phagocyte accumulation in the lungs of patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis (IPF) was investigated. Bronchoalveolar lavage (BAL) fluids from 12 patients with IPF and 15 with sarcoidosis were concentrated by reversed-phase chromatography, and their IL-8 and MCP-1 concentrations assessed by enzyme-linked immunosorbent assay (ELISA), chemotaxis, and enzyme-releasing assays with monocytes and neutrophils. ELISA revealed significantly elevated concentrations of MCP-1 (20.1 ng/mg albumin) in the BAL fluids of patients with pulmonary sarcoidosis and those with IPF (41.8 ng/mg) in comparison to 11 normal individuals (4.24 ng/mg) and 15 patients with chronic bronchitis (CB) (5.16 ng/mg). Similarly, the chemotactic activity for monocytes (MCP-1 equivalent) was strongly increased in patients with sarcoidosis (86.03 ng/mg) as well as in those with IPF (54.47 ng/mg). The chemoattractant activity of normal individuals and CB patients was 7- or 3-fold lower, respectively. Patients with IPF and sarcoidosis also had elevated IL-8 levels (15.5 and 26.0 ng/mg, respectively; normals: 2.14 ng/mg; and CB patients: 4.23 ng/mg) and greater neutrophil chemotaxis (60.25 and 49.68 ng/mg, respectively; normals: 0.35 ng/mg; and CB patients: 11.06 ng/mg). These data suggest that increased levels of both MCP-1 and IL-8 may be characteristic for sarcoidosis or IPF. It appears likely that both of these chemoattractants contribute to the influx of monocytes and neutrophils into the pulmonary alveolus and interstitium in these diseases.

Topics: Adult; Bronchitis; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography; Chronic Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Hexosaminidases; Humans; Interleukin-8; Middle Aged; Monocytes; Neutrophils; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Sensitivity and Specificity; Severity of Illness Index