interleukin-8 and Alveolitis--Extrinsic-Allergic

Hypersensitivity pneumonitis (HP) is an interstitial lung disease, characterized by lung inflammation (non-fibrotic HP) that may often progresses to fibrosis (Fibrotic HP). The tumor necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) can be found as soluble (sol) and transmembrane (tm) forms, playing pro-inflammatory functions but also has been related to immune regulatory functions. Bronchioalveolar lavage from fibrotic and non-fibrotic HP patients was obtained, and immune cells were characterized by flow cytometry, whereas soluble proteins were analyzed by ELISA. Compare to fibrotic HP patients, HP patients with non-fibrotic disease have accumulation of pro-inflammatory CD3+ myeloid cells, cell subpopulations that have decreased tmTNFR2 expression, and low frequency of regulatory-T cells. Whereas solTNF, solTNFR2, and IL-8 are increased. These findings suggest that the TNF pathway may explain, at least partially, the differences between both HP clinical forms. The evaluation of the TNF family molecules may help to develop new therapeutic approaches.

Topics: Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; CD3 Complex; Female; Humans; Interleukin-8; Leukocytes; Lung; Male; Membrane Proteins; Middle Aged; Myeloid Cells; Pneumonia; Pulmonary Fibrosis; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; T-Lymphocytes, Regulatory; Tumor Necrosis Factor-alpha

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

Extrinsic allergic alveolitis (EAA) and idiopathic pulmonary fibrosis (IPF) share the presence of varying degree interstitial involvement and fibrosis. Vascular changes were often reported to accompany the development of fibrosis.. The aim of our study was to examine the differences in angiostatic and angiogenic chemokine milieu in both diseases. Correlations between chemokine levels in bronchoalveolar lavage fluid (BALF), expression of chemokine receptors on CD4+ T cells (CXCR2, CXCR3) in BALF and HRCT pattern of the diseases were investigated.. Sixteen patients with chronic EAA and 8 with IPF were enrolled to the study. Concentrations of interleukin (IL)-8, epithelial neutrophil activating protein (ENA)-78, interferon-gamma-inducible protein (IP)-10 and interferon-inducible T cell alpha chemoattractant (I-TAC) in BALF supernatants were quantified using Fluorokine MultiAnalyte profiling.. There was no significant difference in the BALF chemokine levels between the EAA and IPF group. IL-8 BALF concentrations correlate with the extent of fibrosis in both EAA and IPF (p<0.01). The IP-10 BALF concentrations do not correlate either with the HRCT alveolar or interstitial score and should be evaluated in the relationship with the disease course.. Both IL-8 and ENA-78 probably play a different role in IPF and chronic EAA pathogenesis. While we suggest ENA-78 as the marker of at least partial reversibility of the lung impairment in the EAA patients, IL-8 could be rather an indicator of continuous exposition to provoking agent in EAA patients. IL-8 might serve as a potential marker of early phase of IPF.

Topics: Adult; Aged; Aged, 80 and over; Alveolitis, Extrinsic Allergic; Biomarkers; Bronchoalveolar Lavage Fluid; Chemokine CXCL10; Chemokine CXCL11; Chemokine CXCL5; Chemokines; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Lung; Male; Middle Aged; Prognosis; Prospective Studies; Receptors, Chemokine; Young Adult

To study some indicators of cytokine status among the patients with pneumonia alveolitis 89 patients have been examined. 60 of those patients suffer from exogenous allergic alveolitis (EAA) and - 60 from idiopathic fibrosing alveolitis (IFA). The average age is 36.4+/-3.0. The patients were devided into three groups: I group - 21 (23.6%) patients with acute disease, II group - 25 (28.1%) patients with subacute disease, III group - 43 (48.3%) patients with chronic disease. The level of IL-1beta and IL-8 in blood serum and bronchoalveolar wash-out (BWO) measured by IFA test system. It is identified that the contents of IL-1beta in blood serum of EAA patients exceeded on 7.2%, the contents of IL-8 exceeded on 14.6% among IFA patients - reliable rise IL-1beta on 35.4% (<0.05) and IL-8 on 31.6% (<0.05). The level of proinflammatory cytokines (IL-1beta and IL-8) in peripheric blood corresponded with the level of disease. Along with progressing of disease the contents of cytokine in respiratory space, too high, increased among 21 patients with acute disease, in 13 cases (61.9%) BWO was high in IL-1beta and in 80.8% cases of IL-8. in II group among 25 patients with subacute disease high level of IL-1beta marked in 56.0%, Il-8 in 84% cases; patients in III group high concentration of IL-1beta registered in 51.2%; Il-8 in 81.4% of patients.

Topics: Adult; Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Cytokines; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-1beta; Interleukin-8; Male

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

Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes that cause farmer's lung disease. The early response to Ag is an increase in neutrophils in the lung, whereas the late response is a typical Th1-type granulomatous disease. Many patients who develop disease report a recent viral respiratory infection. These studies were undertaken to determine whether viruses can augment the inflammatory responses in HP. C57BL/6 mice were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) for 3 consecutive days per wk for 3 wk. Some mice were exposed to SR at 2 wk after infection with respiratory syncytial virus (RSV), whereas others were exposed to SR after exposure to saline alone or to heat-inactivated RSV. SR-treated mice developed a typical, early neutrophil response and a late granulomatous inflammatory response. Up-regulation of IFN-gamma and IL-2 gene expression was also found during the late response. These responses were augmented by recent RSV infection but not by heat-inactivated RSV. Mice with a previous RSV infection also had a greater early neutrophil response to SR, with increased macrophage inflammatory protein-2 (MIP-2, murine equivalent of IL-8) release in bronchoalveolar lavage fluid. These studies suggest that viral infection can augment both the early and late inflammatory responses in HP.

Topics: Alveolitis, Extrinsic Allergic; Animals; Bronchoalveolar Lavage Fluid; Female; Granuloma, Respiratory Tract; Interleukin-8; Leukocyte Count; Mice; Mice, Inbred C57BL; Neutrophils; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Saccharopolyspora

The alveolar macrophage (AM) secretes interleukin 1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), all of them inflammatory cytokines involved in the pathogenesis of many lung diseases. The aim of the present work was to evaluate the basal and stimulated secretion of these cytokines by human AMs. Human AMs were collected by bronchoalveolar lavage (BAL) from four healthy controls and 13 patients with diffuse interstitial lung disease (five cases of sarcoidosis, three of hypersensitivity pneumonitis and five of idiopathic pulmonary fibrosis). AMs were cultured in the presence or absence of different concentrations of lipopolysaccharide (LPS), phorbolmyristate and gamma-interferon. IL-1beta, TNF-alpha, IL-6 and IL-8 levels were measured in BAL fluid and culture supernatant using specific enzyme-linked immunosorbent assays. The substance found to stimulate the secretion of inflammatory cytokines to the greatest extent was LPS at a concentration of 10 microg/ml. Regarding the secretion of IL-1beta, four observations were of interest: basal secretion was very low; LPS exerted a potent stimulatory effect; considerable within-group variability was observed; and there were no significant differences in the comparisons among groups. With respect to TNF-alpha secretion, the results were similar. The only striking finding was the higher basal secretion of this cytokine with respect to that of IL-1beta. Regarding the secretion of IL-6, the same pattern followed by TNF-alpha was found. However, it should be stressed that the increase induced by LPS was smaller than in the two previous cytokines. Regarding the secretion of IL-8, three findings were patent: the strong basal secretion of this cytokine; the moderate increase induced by LPS; and the existence of significant differences among the different groups with respect to the stimulated secretion of this cytokine, which reached maximum values in patients with idiopathic pulmonary fibrosis. Finally, it should be noted that the pattern of cytokines observed in the BAL fluid was similar to that found in cultured AM supernatants. The pattern of inflammatory cytokine secretion by AMs differs from that of other cells of the mononuclear phagocyte system (MPS). In this sense. AMs secrete low amounts of IL-1, moderate amounts of TNF-alpha and IL-6, and high quantities of IL-8. Adherence is an important stimulus in the secretion of these molecules and LPS elicits an incr

Topics: Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cells, Cultured; Chemokines; Cough; Humans; Interferon-gamma; Interleukin-1; Interleukin-6; Interleukin-8; Lipopolysaccharides; Macrophages, Alveolar; Pulmonary Fibrosis; Reference Values; Sarcoidosis; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Cyclosporin A (CsA) is an immunomodulator drug that has been used in the treatment of several types of advanced pulmonary interstitial disease. This beneficial effect occurs mainly in circumstances in which alveolitis due to CD4 lymphocytes is absent, suggesting that CsA acts on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by human alveolar macrophages (AMs). Human AMs were collected by bronchoalveolar lavage from four control subjects and 13 patients with interstitial lung disease. Purified human AMs were incubated with different concentrations of CsA (200, 20 and 2 ng ml-1) in the presence or absence of lipopolysaccharide (LPS). Interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. It was found that CsA inhibits basal secretion of TNF-alpha and IL-8 at 20 and 200 ng ml-1. However, none of the different concentrations of CsA modified basal secretion of IL-1 beta nor IL-6. By contrast, a lower concentration of CsA (2 ng ml-1) inhibits LPS-stimulated secretion of all inflammatory cytokines. It is concluded that CsA exerts a modest effect on inflammatory cytokine production by human AMs.

Topics: Alveolitis, Extrinsic Allergic; Cells, Cultured; Cyclosporine; Cytokines; Humans; Immunosuppressive Agents; Interleukin-1; Interleukin-6; Interleukin-8; Lipopolysaccharides; Lung Diseases, Interstitial; Macrophages, Alveolar; Pulmonary Fibrosis; Sarcoidosis; Tumor Necrosis Factor-alpha

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

We examined the synthesis and release of the proinflammatory cytokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and interleukin-8 (IL-8) in the context of subjects with hypersensitivity pneumonitis (HP). Subjects with acute HP were found to have alveolar macrophages that released high levels of MIP-1 alpha and IL-8, whereas control subjects had cells that released low levels of these factors. Bronchoalveolar lavage fluid from HP subjects contained low but significant levels of MIP-1 alpha and IL-8. Immunohistochemistry revealed that macrophages from acute HP subjects expressed MIP-1 alpha and IL-8 at high levels. Treatment of acute HP subjects by contact avoidance or by corticosteroids reduced the synthesis of both cytokines. Supernatants of alveolar macrophages from subjects with HP were shown to attract activated CD8+ T lymphocytes, and this activity was significantly inhibited by anti-MIP-1 alpha. MIP-1 alpha and IL-8 may be important inflammatory cytokines in the development of HP via their capacity to attract inflammatory cells (activated CD8+ T lymphocytes and neutrophils, respectively) into the airways of subjects with HP.

Topics: Acute Disease; Adult; Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; CD8-Positive T-Lymphocytes; Chemokine CCL4; Chemotaxis, Leukocyte; Cytokines; Enzyme-Linked Immunosorbent Assay; Farmer's Lung; Female; Humans; Immunohistochemistry; Interleukin-8; Macrophage Inflammatory Proteins; Macrophages, Alveolar; Male; Middle Aged; Monokines

Our previous study demonstrated increased levels of C5a des Arg and increased numbers of neutrophils in bronchoalveolar lavage (BAL) fluids of patients acutely ill with hypersensitivity pneumonitis (HP), suggesting that complement fragments activated by immune complexes (IC) play a role in the early stage of disease. The present study was undertaken to clarify the mechanisms involved in lung injury produced by IC formed in the airway. Sequential changes of neutrophils and neutrophil chemotactic activities (NCF) in BAL fluids were evaluated in guinea-pigs injected intratracheally with preformed IC. Our results were as follows: 1) There was an increased number of neutrophils in BAL cells within 48 hours of the intratracheal injection with preformed IC reaching a peak at 24 hours postinjection. 2) NCF in BAL fluids were potent at 2-6 hours postinjection and preceded an increase of neutrophils in BAL cells, indicating that NCF play a role in the accumulation of neutrophils in the lung. 3) A consequent increase of alveolar macrophages and macrophage chemotactic activities (MCF) in BAL fluids was observed but to a lesser extent. 4) Pretreatment with cobra venom factor of guinea-pigs reduced the increase of BAL cells, especially neutrophils and NCF to approximately 60% of comparable results, suggesting that complement fragments play a role in IC mediated lung injury.

Topics: Alveolitis, Extrinsic Allergic; Animals; Antigen-Antibody Complex; Bronchoalveolar Lavage Fluid; Chemotactic Factors; Female; Guinea Pigs; Interleukin-8; Neutrophils

Hypersensitivity pneumonitis (HP) is believed to be induced by immunological mechanisms, the details of which remain to be clarified. While a role for cellular immunity is accepted in the pathogenesis of HP, several clinical observations also suggest a role for immune-complex-mediated lung injury. We have previously demonstrated the presence of chemotactic factors for polymorphonuclear cells (PMNs) in bronchoalveolar lavage (BAL) fluids of acutely ill patients with the summer type of HP found in Japan. The present study correlated chemotactic factors for PMNs with the level of C5a des Arg in BAL fluids obtained from patients with summer type HP. Furthermore, this study demonstrated that PMNs were increased in BAL fluids obtained after 2 days of avoidance of exposure to the presumptive causative agent. The percentage of PMNs in the BAL increased in proportion to the activity of the chemotactic factors. Finally, leukotriene B4 was not detected in concentrated BAL or supernatant fluids of cultured macrophages. These results suggest that complement activation in the respiratory tract may occur as the early event in the pathogenesis of HP.

Topics: Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage Fluid; Chemotactic Factors; Complement Activation; Complement C3; Complement C3a; Complement C5; Complement C5a, des-Arginine; Complement System Proteins; Humans; Interleukin-8; Leukotriene B4; Neutrophils; Proteins