interleukin-8 and Idiopathic-Pulmonary-Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that affects 3 million people worldwide. Senescence and small extracellular vesicles (sEVs) have been implicated in the pathogenesis of IPF, although how sEVs promote disease remains unclear. Here, we profile sEVs from bronchial epithelial cells and determine small RNA (smRNA) content.. Conditioned media was collected and sEVs were isolated from normal human bronchial epithelial cells (NHBEs) and IPF-diseased human bronchial epithelial cells (DHBEs).. Increased sEV release from DHBEs compared to NHBEs (n = 4; p < 0.05) was detected by nanoparticle tracking analysis. NHBEs co-cultured with DHBE-derived sEVs for 72 h expressed higher levels of SA-β-Gal and γH2AX protein, p16 and p21 RNA and increased secretion of IL6 and IL8 proteins (all n = 6-8; p < 0.05). sEVs were also co-cultured with healthy air-liquid interface (ALI) cultures and similar results were observed, with increases in p21 and p16 gene expression and IL6 and IL8 (basal and apical) secretion (n = 6; p < 0.05). Transepithelial electrical resistance (TEER) measurements, a reflection of epithelial barrier integrity, were decreased upon the addition of DHBE-derived sEVs (n = 6; p < 0.05). smRNA-sequencing identified nineteen significantly differentially expressed miRNA in DHBE-derived sEVs compared to NHBE-derived sEVs, with candidate miRNAs validated by qPCR (all n = 5; p < 0.05). Four of these miRNAs were upregulated in NHBEs co-cultured with DHBE-derived sEVs and three in healthy ALI cultures co-cultured with DHBE-derived sEVs (n = 3-4; p < 0.05).. This data demonstrates that DHBE-derived sEVs transfer senescence to neighbouring healthy cells, promoting the disease state in IPF.

Topics: Extracellular Vesicles; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-6; Interleukin-8; MicroRNAs

Topics: B7-H1 Antigen; Cell Proliferation; Cellular Senescence; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Mesenchymal Stem Cells; Programmed Cell Death 1 Receptor

Idiopathic pulmonary fibrosis is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. Interleukin (IL)-11 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. In this study, we explore whether a potential antifibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and antifibrotic effects through suppressing activation of the IL-11/MEK/ERK signaling pathway in vivo and in vitro. Male C57BL/6 J mice were intratracheally injected with bleomycin or saline. Fluorofenidone was administered throughout the course of the experiment. Lung tissue sections were stained with hemotoxylin and eosin, and Masson trichrome. Cytokines were measured using the enzyme-linked immunosorbent assay. The α-smooth muscle actin (α-SMA), fibronectin, and collagen I were measured using immunohistochemistry, and the phosphorylated extracellular signal-regulated kinase, phosphorylated mitogen-activated protein kinase, IL-11RA, and gp130 were measured using Western blot. The RAW264.7 cells and the normal human lung fibroblasts were treated with IL-11 and/or FD, IL-11RA-siRNA, or MEK inhibitor. The expressions of phosphorylated extracellular signal-regulated kinase, phosphorylated mitogen-activated protein kinase, IL-11RA, gp130, α-SMA, fibronectin, and collagen I were measured using Western blot and/or real-time polymerase chain reaction, and the cytokines were measured using enzyme-linked immunosorbent assay. Results showed that FD markedly reduced the expressions of IL-8, IL-18, IL-11, monocyte chemotactic protein-1, α-SMA, fibronectin, and collagen I in mice lung tissues. In addition, FD attenuated IL-11-induced expressions of α-SMA, fibronectin, and collagen I and inhibited IL-11RA, gp130, and phosphorylation of the ERK and MEK protein expression, as well as reduced the expressions of IL-8, IL-18, and monocyte chemotactic protein-1 in vitro. This study demonstrated that FD attenuated bleomycin-induced pulmonary inflammation and fibrosis in mice by inhibiting the IL-11/MEK/ERK signaling pathway.

Topics: Actins; Animals; Anti-Inflammatory Agents; Bleomycin; Chemokine CCL2; Collagen; Cytokine Receptor gp130; Eosine Yellowish-(YS); Extracellular Signal-Regulated MAP Kinases; Fibronectins; Fibrosis; Hematoxylin; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-11; Interleukin-18; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases; Pneumonia; Pyridones; RNA, Small Interfering; Signal Transduction

Genes involved in lung development may become dysregulated in adult life and contribute to the pathogenesis of lung diseases. Multiple genes regulate lung development, including Forkhead box protein P1-4 (FoxP1-4).. We examined the association between variants in the FoxP1-4 genes and lung function using data from a GWAS that included close to 400,000 individuals and 20 million SNPs.. More than 100 variants in the FoxP1 gene, but none in the FoxP2-4 genes, are associated with lung function. The sentinel variant in the FoxP1 gene associated with FEV1 was rs1499894 (C > T), while the sentinel variant in the FoxP1 gene associated with FVC was rs35480566 (A > G). Those with the T allele instead of the C allele for rs1499894, or the G allele instead of the A allele for rs35480566 had increased FoxP1 mRNA levels in transcriptomic data, higher FEV1 and FVC, and reduced odds of being diagnosed with idiopathic pulmonary fibrosis. Further, knockdown of FoxP1 in lung epithelial cells by RNA interference led to increased mRNA levels for matrix metalloproteinases 1, 2, 3 and pro-inflammatory cytokines IL-6 & IL-8, as well as reduced cell viability after exposure to cigarette smoke-all processes implicated in the pathogenesis of COPD and IPF.. Our results suggest that the protein encoded by the FoxP1 gene may protect against the development of COPD and IPF. A causal role for FoxP1 in the pathogenesis of COPD and IPF may warrant further investigation, and FoxP1 may be a novel therapeutic target for these lung disorders.

Topics: Adult; Forkhead Transcription Factors; Humans; Idiopathic Pulmonary Fibrosis; Inflammation Mediators; Interleukin-6; Interleukin-8; Lung; Matrix Metalloproteinases; Pulmonary Disease, Chronic Obstructive; Repressor Proteins; RNA, Messenger

Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.. In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.. These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.

Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Particulate Matter; Pulmonary Alveoli; SARS-CoV-2; Serine Endopeptidases; Up-Regulation

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. We previously identified fibrogenic mesenchymal progenitor cells (MPCs) in the lungs of patients with IPF who serve as drivers of progressive fibrosis. Recent single-cell RNA sequencing work revealed that IPF MPCs with the highest transcriptomic network entropy differ the most from control MPCs and that increased CD44 was a marker of these IPF MPCs. We hypothesize that IPF MPCs with high CD44 (CD44hi) expression will display enhanced fibrogenicity. We demonstrate that CD44-expressing MPCs are present at the periphery of the IPF fibroblastic focus, placing them in regions of active fibrogenesis. In a humanized mouse xenograft model, CD44hi IPF MPCs are more fibrogenic than CD44lo IPF MPCs, and knockdown of CD44 diminishes their fibrogenicity. CD44hi IPF MPCs display increased expression of pluripotency markers and enhanced self-renewal compared with CD44lo IPF MPCs, properties potentiated by IL-8. The mechanism involves the accumulation of CD44 within the nucleus, where it associates with the chromatin modulator protein Brahma-related gene 1 (Brg1) and the zinc finger E-box binding homeobox 1 (Zeb1) transcription factor. This CD44/Brg1/Zeb1 nuclear protein complex targets the Sox2 gene, promoting its upregulation and self-renewal. Our data implicate CD44 interaction with the epigenetic modulator protein Brg1 in conveying IPF MPCs with cell-autonomous fibrogenicity.

Topics: Adoptive Transfer; Animals; Cell Self Renewal; DNA Helicases; Humans; Hyaluronan Receptors; Idiopathic Pulmonary Fibrosis; Interleukin-8; Lung; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Nuclear Proteins; SOXB1 Transcription Factors; Transcription Factors; Zinc Finger E-box-Binding Homeobox 1

Mounting evidence from the literature suggests that blocking S1P2 receptor (S1PR2) signaling could be effective for the treatment of idiopathic pulmonary fibrosis (IPF). However, only a few antagonists have been so far disclosed. A chemical enablement strategy led to the discovery of a pyridine series with good antagonist activity. A pyridazine series with improved lipophilic efficiency and with no CYP inhibition liability was identified by scaffold hopping. Further optimization led to the discovery of

Topics: Animals; CHO Cells; Cricetulus; Drug Design; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Male; Mice; Pyridazines; Sphingosine-1-Phosphate Receptors; Structure-Activity Relationship; Tissue Distribution

Secretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-β and IL-8.

Topics: A549 Cells; Aged; Aged, 80 and over; Antigens, CD; Epithelial Cells; Female; Gene Expression Regulation, Neoplastic; Humans; Idiopathic Pulmonary Fibrosis; Immunoglobulin A, Secretory; Interleukin-8; Lung; Male; Middle Aged; Receptors, Transferrin; RNA Interference; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties.. ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis.. To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.

Topics: Adult; Cells, Cultured; Cohort Studies; Endothelial Cells; Follow-Up Studies; France; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Phenotype; Primary Cell Culture; Stem Cells

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease, with high mortality. Currently, the aetiology and the pathology of IPF are poorly understood, with both innate and adaptive responses previously being implicated in the disease pathogenesis. Heat shock proteins (Hsp) and antibodies to Hsp in patients with IPF have been suggested as therapeutic targets and prognostic biomarkers, respectively. We aimed to study the relationship between the expression of Hsp72 and anti-Hsp72 antibodies in the BAL fluid and serum Aw disease progression in patients with IPF.. A novel indirect ELISA to measure anti-Hsp72 IgG was developed and together with commercially available ELISAs used to detect Hsp72 IgG, Hsp72 IgGAM, and Hsp72 antigen, in the serum and BALf of a cohort of IPF (. Anti-Hsp72 IgG was detectable in the serum and BALf of IPF (. Our results indicate that intrapulmonary anti-Hsp72 antibodies are associated with improved outcomes in IPF. These may represent natural autoantibodies, and anti-Hsp72 IgM and IgA may provide a beneficial role in disease pathogenesis, though the mechanism of action for this has yet to be determined.

Topics: Adult; Aged; Aged, 80 and over; Alveolar Epithelial Cells; Autoantibodies; Cells, Cultured; Chemokines, CC; Disease Progression; Female; HSP72 Heat-Shock Proteins; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Lung; Macrophages; Male; Middle Aged; Survival Analysis

Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients.. Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied.. Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines.. High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.

Topics: Acute Disease; Aged; Biomarkers; Cytokines; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-6; Interleukin-8; Male; Survival Analysis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease, but the mechanisms driving progression remain incompletely defined. We previously reported that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs), which serve as a cell of origin for IPF fibroblasts. Proliferating IPF MPCs are located at the periphery of fibroblastic foci in an active cellular front at the interface between the myofibroblast-rich focus core and adjacent normal alveolar structures. Among a large set of genes that distinguish IPF MPCs from their control counterparts, we identified IL-8 as a candidate mediator of IPF MPC fibrogenicity and driver of fibrotic progression. IPF MPCs and their progeny displayed increased steady-state levels of IL-8 and its cognate receptor CXCR1 and secreted more IL-8 than did controls. IL-8 functioned in an autocrine manner promoting IPF MPC self-renewal and the proliferation and motility of IPF MPC progeny. Secreted IL-8 also functioned in a paracrine manner stimulating macrophage migration. Analysis of IPF lung tissue demonstrated codistribution of IPF MPCs with activated macrophages in the active cellular front of the fibroblastic focus. These findings indicate that IPF MPC-derived IL-8 is capable of expanding the mesenchymal cell population and recruiting activated macrophages cells to actively evolving fibrotic lesions.

Topics: Cell Movement; Cell Proliferation; Cells, Cultured; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Mesenchymal Stem Cells; Signal Transduction

Pulmonary hypertension (PH) complicates the care of patients with chronic lung disease, such as idiopathic pulmonary fibrosis (IPF), resulting in a significant increase in morbidity and mortality. Disease pathogenesis is orchestrated by unidentified myeloid-derived cells. We used murine models of PH and pulmonary fibrosis to study the role of circulating myeloid cells in disease pathogenesis and prevention. We administered clodronate liposomes to bleomycin-treated wild-type mice to induce pulmonary fibrosis and PH with a resulting increase in circulating bone marrow-derived cells. We discovered that a population of C-X-C motif chemokine receptor (CXCR) 2

Topics: Animals; Arginase; Bleomycin; Cell Movement; Clodronic Acid; Female; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Interleukin-8; Male; Mice; Mice, Inbred C57BL; Myeloid Cells; Myeloid-Derived Suppressor Cells; Nitric Oxide Synthase Type II; Phenylurea Compounds; Receptors, Interleukin-8B

Panax notoginseng saponin (PNS) constitutes the major effective components of Panax notoginseng, which is widely used to treat microcirculatory disturbance associated diseases. In this study, we designed to investigate the effect of PNS on the treatment of pulmonary fibrosis (PF) and further explored its mechanism. A total of 40 healthy Japanese White rabbits were randomly divided into five groups (control group; PF model group; PNS prevention group; PNS treatment group; and western medicine [prednisone acetate] treatment group). Expression of hydroxyproline (HYP), fibronectin (FN), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), interleukin-6 (IL-6), and interleukin-8 (IL-8) in serum was detected using corresponding detection kits. Western blot was applied to detect the expression of p50 and p65 in pulmonary tissues. The pathological variations of the cardiac and pulmonary ultrastructure were observed under both the optical and electron microscope. PF models were established successfully. The results showed that compared with the other groups, PNS groups (PNS prevention and treatment group) apparently relieved the cardiopulmonary injury, and reduced IL-6 and IL-8 expression levels in the serum. Furthermore, the PNS groups performed better in relieving cardiopulmonary injurythan other groups. Both the PNS groups and the western medicine treatment group presented an obvious role in relieving PF. We concluded that PNS could reduce the expression of AST, LDH, CK, IL-6, and IL-8 in serum of the rabbits, relieve the pathological ultrastructure of cardiopulmonary injury, alleviate PF. And it might be attributed to the inhibition on the NF-κB signaling pathway.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Creatine Kinase; Disease Models, Animal; Idiopathic Pulmonary Fibrosis; Interleukin-6; Interleukin-8; L-Lactate Dehydrogenase; NF-kappa B; Panax notoginseng; Phytotherapy; Prednisone; Rabbits; Saponins; Signal Transduction; Treatment Outcome

There is accumulating evidence to indicate that long non-coding RNAs (lncRNAs) are important regulators of the inflammatory response. In this report, we have employed next generation sequencing to identify 14 lncRNAs that are differentially expressed in human lung fibroblasts following the induction of inflammation using interleukin-1β (IL-1β). Knockdown of the two most highly expressed lncRNAs, IL7AS, and MIR3142HG, showed that IL7AS negatively regulated IL-6 release whilst MIR3142HG was a positive regulator of IL-8 and CCL2 release. Parallel studies in fibroblasts derived from patients with idiopathic pulmonary fibrosis showed similar increases in IL7AS levels, that also negatively regulate IL-6 release. In contrast, IL-1β-induced MIR3142HG expression, and its metabolism to miR-146a, was reduced by 4- and 9-fold in IPF fibroblasts, respectively. This correlated with a reduced expression of inflammatory mediators whilst MIR3142HG knockdown showed no effect upon IL-8 and CCL2 release. Pharmacological studies showed that IL-1β-induced IL7AS and MIR3142HG production and release of IL-6, IL-8, and CCL2 in both control and IPF fibroblasts were mediated via an NF-κB-mediated pathway. In summary, we have cataloged those lncRNAs that are differentially expressed following IL-1β-activation of human lung fibroblasts, shown that IL7AS and MIR3142HG regulate the inflammatory response and demonstrated that the reduced inflammatory response in IPF fibroblast is correlated with attenuated expression of MIR3142HG/miR-146a.

Topics: Cells, Cultured; Chemokine CCL2; Female; Fibroblasts; Gene Expression Profiling; Gene Expression Regulation; Humans; Idiopathic Pulmonary Fibrosis; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; RNA, Long Noncoding

Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with inflammation. To restore this balance, antioxidants are often suggested as therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous antioxidant quercetin, which has a versatile antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of quercetin on oxidative and inflammatory markers in IPF. Here, we demonstrate that IPF patients have a significantly reduced endogenous antioxidant defense, shown by a reduced total antioxidant capacity and lowered glutathione and uric acid levels compared to healthy controls. This confirms that the redox balance is disturbed in IPF. Ex vivo incubation with quercetin in blood of both IPF patients and healthy controls reduces LPS-induced production of the pro-inflammatory cytokines IL-8 and TNFα. This anti-inflammatory effect was more pronounced in the blood of the patients. Our pro-fibrotic in vitro model, consisting of bleomycin-triggered BEAS-2B cells, shows that quercetin boosts the antioxidant response, by increasing Nrf2 activity, and decreases pro-inflammatory cytokine production in a concentration-dependent manner. Collectively, our findings implicate that IPF patients may benefit from the use of quercetin to restore the disturbed redox balance and reduce inflammation.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antioxidants; Bleomycin; Case-Control Studies; Cell Line; Dose-Response Relationship, Drug; Female; Humans; Idiopathic Pulmonary Fibrosis; Inflammation Mediators; Interleukin-8; Lung; Male; Middle Aged; NF-E2-Related Factor 2; Oxidation-Reduction; Oxidative Stress; Quercetin; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin leading rapidly to death. This paper addresses the issue of whether sputum induction is a suitable tool to study respiratory tract inflammation and potential biomarkers in IPF compared to COPD, a fibrosing airway wall disease.. In a cross-sectional analysis, 15 IPF patients, 32 COPD and 30 healthy subjects underwent sputum induction. Total sputum cell counts and the amount of TGF- β, IGF-1, IGF-2, IGFBP-1, IGFBP-2, IGFBP-3, IL-8, IL-13, MMP-7, MMP-9, YKL-40, TNF-α and KL-6 in sputum supernatant were analysed. We also profiled gene expression of cells in the induced sputum for TGF-β, MMP-7, YKL-40, IGFBP-2, IL-6, IL-8 and TNF-α.. IPF patients, like COPD, had increased sputum absolute number of neutrophils, eosinophils, macrophages and epithelial cells compared to HS. IPF sputum supernatants had increased concentrations of IGFBP-2, IL-8, TGF-β, MMP-7, MMP-9 and KL-6 (p<0.05, p<0.0001, p<0.05, p<0.05, p<0.0001, p<0.05 respectively) when compared to healthy subjects where COPD had higher IL-6 and TNF-α levels than IPF (p<0.05 and p<0.05 respectively) and HS (p<0.0001 and p<0.001 respectively) and higher IL-8 and MMP-9 than HS (p<0.0001 and p<0.001 respectively). Conversely to IL-6 and TNF-α, MMP-7 was increased in IPF compared to COPD (p<0.05). The KL-6 and MMP-7 protein levels in sputum were inversely correlated with total lung capacity (TLC, % of predicted) in IPF patients (r = -0.73 and r = -0.53 respectively). Sputum gene expression analysis identified a significant increase for IGFBP-2, IL-6, IL-8 and MMP-7 in IPF compared to HS (p<0.05, p<0.01, p<0.05 and p<0.0001 respectively) and for IGFBP-2, YKL-40, IL-6, IL-8 and MMP-7 compared to COPD (p<0.01, p<0.01, p<0.05, p<0.01 and p<0.0001 respectively). Furthermore, gene expression of TGF-β was increased in IPF compared to COPD (p<0.001) but not to HS.. Our data show clear increase in expression and production of IGFBP-2, IL-8 and MMP-7 in sputum from patients with IPF that may contribute to the disease.

Topics: Biomarkers; Cross-Sectional Studies; Female; Gene Expression; Humans; Idiopathic Pulmonary Fibrosis; Insulin-Like Growth Factor Binding Protein 2; Interleukin-8; Leukocyte Count; Male; Matrix Metalloproteinase 7; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Sputum

Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention.

Topics: Animals; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Dog Diseases; Dogs; Female; Idiopathic Pulmonary Fibrosis; Interleukin-8; Lung; Male

The West Highland white terrier (WHWT) is particularly prone to canine idiopathic pulmonary fibrosis (CIPF). We hypothesized that higher circulating concentrations of chemokines CXCL8, CCL2, serotonin (5-HT), or vascular endothelial growth factor (VEGF) could serve as predisposing factors for CIPF development in the WHWT breed. Serum samples from 103 healthy dogs of seven different breeds variably predisposed to CIPF were collected. Serum CXCL8 concentrations were higher in healthy WHWT compared with each of the other groups of healthy dogs. Serum CCL2 concentrations were higher in healthy WHWT and Maltese compared with King Charles spaniels and Malinois Belgian shepherds. No relevant inter-breed differences were observed for serum 5-HT concentrations regarding CIPF predisposition. VEGF values from 89.3% of samples tested were below the kit detection limit. In conclusion, high CXCL8 blood concentrations and possibly CCL2 concentrations might be related to the breed predisposition of the WHWT for CIPF and warrants further investigations.

Topics: Animals; Chemokine CCL2; Dog Diseases; Dogs; Genetic Predisposition to Disease; Genotype; Idiopathic Pulmonary Fibrosis; Interleukin-8; Serotonin; Species Specificity; Vascular Endothelial Growth Factor A

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

Diverse autoantibodies are present in most patients with idiopathic pulmonary fibrosis (IPF). We hypothesized that specific autoantibodies may associate with IPF manifestations.. To identify clinically relevant, antigen-specific immune responses in patients with IPF.. Autoantibodies were detected by immunoblots and ELISA. Intrapulmonary immune processes were evaluated by immunohistochemistry. Anti-heat shock protein 70 (HSP70) IgG was isolated from plasma by immunoaffinity. Flow cytometry was used for leukocyte functional studies.. HSP70 was identified as a potential IPF autoantigen in discovery assays. Anti-HSP70 IgG autoantibodies were detected by immunoblots in 3% of 60 control subjects versus 25% of a cross-sectional IPF cohort (n = 122) (P = 0.0004), one-half the patients with IPF who died (P = 0.008), and 70% of those with acute exacerbations (P = 0.0005). Anti-HSP70 autoantibodies in patients with IPF were significantly associated with HLA allele biases, greater subsequent FVC reductions (P = 0.0004), and lesser 1-year survival (40 ± 10% vs. 80 ± 5%; hazard ratio = 4.2; 95% confidence interval, 2.0-8.6; P < 0.0001). HSP70 protein, antigen-antibody complexes, and complement were prevalent in IPF lungs. HSP70 protein was an autoantigen for IPF CD4 T cells, inducing lymphocyte proliferation (P = 0.004) and IL-4 production (P = 0.01). IPF anti-HSP70 autoantibodies activated monocytes (P = 0.009) and increased monocyte IL-8 production (P = 0.049). ELISA confirmed the association between anti-HSP70 autoreactivity and IPF outcome. Anti-HSP70 autoantibodies were also found in patients with other interstitial lung diseases but were not associated with their clinical progression.. Patients with IPF with anti-HSP70 autoantibodies have more near-term lung function deterioration and mortality. These findings suggest antigen-specific immunoassays could provide useful clinical information in individual patients with IPF and may have implications for understanding IPF progression.

Topics: Aged; Antigen-Antibody Complex; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; HSP70 Heat-Shock Proteins; Humans; Idiopathic Pulmonary Fibrosis; Immunoglobulin G; Immunohistochemistry; Interleukin-4; Interleukin-8; Linear Models; Lung; Male; Prognosis; Proportional Hazards Models

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology with a variable and unpredictable course.. The aim of this study was to identify and validate plasma proteins that are predictive of outcome in IPF.. Plasma samples were available for 241 patients with IPF (140 derivation and 101 validation). In the derivation cohort, concentrations of 92 proteins were analyzed using a multiplex bead-based immunoassay and concentrations of matrix metalloproteinase (MMP)-7, MMP-1, and surfactant protein D were assessed by ELISA. In the validation cohort concentrations of intercellular adhesion molecule (ICAM)-1, IL-8, and vascular cell adhesion molecule (VCAM)-1 were assessed by bead-based multiplex assay, and S100A12 and MMP-7 by ELISA. Associations of biomarkers with mortality, transplant-free survival, and disease progression were tested in the derivation and validation cohorts using nonparametric methods of survival analysis and the Cox proportional hazards model, and an integrated risk prediction score was derived and tested.. High concentrations of MMP-7, ICAM-1, IL-8, VCAM-1, and S100A12 predicted poor overall survival, poor transplant-free survival, and poor progression-free survival in the derivation cohort. In the independent validation cohort high concentrations of all five were predictive of poor transplant-free survival; MMP-7, ICAM-1, and IL-8 of overall survival; and ICAM-1 of poor progression-free survival. The personal clinical and molecular mortality prediction index derived in the derivation cohort was highly predictive of mortality in the validation cohort.. Our results suggest that plasma proteins should be evaluated as a tool for prognosis determination in prioritization of patients for lung transplantation and stratification in drug studies.

Topics: Aged; Biomarkers; Cell Adhesion Molecules; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Idiopathic Pulmonary Fibrosis; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 7; Matrix Metalloproteinases; Predictive Value of Tests; Proportional Hazards Models; S100 Proteins; S100A12 Protein; Survival Analysis; Vascular Cell Adhesion Molecule-1

Topics: Cell Adhesion Molecules; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Male; Matrix Metalloproteinases; S100 Proteins; S100A12 Protein

Topics: Cell Adhesion Molecules; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Male; Matrix Metalloproteinases; S100 Proteins

Interleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF.. One promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay.. The minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002).. The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Bronchoalveolar Lavage Fluid; Case-Control Studies; Chi-Square Distribution; Enzyme-Linked Immunosorbent Assay; Female; Gene Frequency; Genes, Reporter; Genetic Predisposition to Disease; HEK293 Cells; Homozygote; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Introns; Logistic Models; Male; Middle Aged; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Proportional Hazards Models; Republic of Korea; Risk Assessment; Risk Factors; Transfection; Up-Regulation

The presence of antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis (Wegener's) (GPA) implicates the neutrophil as a key effector cell. Previous studies have reported elevated neutrophil counts in the lung, although the determinants of neutrophil chemotaxis in the GPA lung are unknown. Bronchoalveolar lavage fluid (BALF) cell counts, myeloperoxidase (MPO) and chemokines were measured in 27 patients with GPA, 20 disease controls with idiopathic pulmonary fibrosis (IPF) and six healthy controls. CXC chemokine ligand (CXCL)8, interleukin (IL)-1β, epithelial neutrophil-activating protein 78, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor were measured by ELISA. The neutrophil chemotactic potential of BALF was investigated using the under-agarose method, and specific antibodies were used to examine the role of CXCL8 and IL-1β. GPA BALF had an increased neutrophil percentage, and elevated MPO, CXCL8 and G-CSF concentrations compared with healthy controls. Chemotaxis of control neutrophils towards BALF from patients with active (p=0.006) and remission (p=0.077) GPA, and IPF (p=0.001) patients was increased compared with normal controls. BALF-induced chemotaxis correlated with BALF IL-1β (r=0.761, p=0.001) and CXCL8 (r=0.640, p=0.012) in GPA, and was inhibited by anti-CXCL8 (85%; p<0.001) and anti-IL-1β (69%; p<0.001). Our study confirms a neutrophilia and pro-inflammatory alveolar milieu that persists in clinical remission. CXCL8 and IL-1β appear to play important roles in the neutrophil chemotactic response to BALF.

Topics: Aged; Bronchoalveolar Lavage Fluid; Chemokine CXCL5; Chemotaxis, Leukocyte; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Granulomatosis with Polyangiitis; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Neutrophils

Adenosine is generated in response to cellular stress and damage and is elevated in the lungs of patients with chronic lung disease. Adenosine signaling through its cell surface receptors serves as an amplifier of chronic lung disorders, suggesting adenosine-based therapeutics may be beneficial in the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Previous studies in mouse models of chronic lung disease demonstrate that the key components of adenosine metabolism and signaling are altered. Changes include an up-regulation of CD73, the major enzyme of adenosine production and down-regulation of adenosine deaminase (ADA), the major enzyme for adenosine metabolism. In addition, adenosine receptors are elevated.. The focus of this study was to utilize tissues from patients with COPD or IPF to examine whether changes in purinergic metabolism and signaling occur in human disease. Results demonstrate that the levels of CD73 and A(2B)R are elevated in surgical lung biopsies from severe COPD and IPF patients. Immunolocalization assays revealed abundant expression of CD73 and the A(2B)R in alternatively activated macrophages in both COPD and IPF samples. In addition, mediators that are regulated by the A(2B)R, such as IL-6, IL-8 and osteopontin were elevated in these samples and activation of the A(2B)R on cells isolated from the airways of COPD and IPF patients was shown to directly induce the production of these mediators.. These findings suggest that components of adenosine metabolism and signaling are altered in a manner that promotes adenosine production and signaling in the lungs of patients with COPD and IPF, and provide proof of concept information that these disorders may benefit from adenosine-based therapeutics. Furthermore, this study provides the first evidence that A(2B)R signaling can promote the production of inflammatory and fibrotic mediators in patients with these disorders.

Topics: 5'-Nucleotidase; Adenosine; Adult; Aged; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-6; Interleukin-8; Lung; Macrophages, Alveolar; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Purinergic P1 Receptor Antagonists; Purines; Pyrazoles; Receptors, Purinergic P1; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription, Genetic

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

alpha-Defensins, antimicrobial peptides produced mainly by neutrophils, have been reported to be associated with a wide variety of lung diseases, including idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and diffuse panbronchiolitis (DPB). In each disease, alpha-defensins are located in different areas, such as around the alveolar septa in IPF and around the airways in CF and DPB, suggesting that alpha-defensins play different roles. Meanwhile, growth factors are known to contribute to IPF, CF, and DPB. alpha-Defensins are known to induce interleukin (IL)-8 in airway epithelial cells, but the effects of alpha-defensins on the release of growth factors from various components in the lung have not been sufficiently investigated. In the present study, the in vitro effects of human neutrophil peptide (HNP)-1 (a subtype of alpha-defensin) on the expressions of IL-8 and growth factors in lung fibroblasts, bronchial epithelial cells, and alveolar epithelial cells were examined. HNP-1 mainly enhanced the expression of IL-8 in epithelial cells, whereas it enhanced transforming growth factor-beta and vascular endothelial growth factor expressions in lung fibroblasts. These results suggest that alpha-defensins play different roles in the pathogenesis of IPF, CF, and DPB according to the location in the lung where the alpha-defensins are mainly produced.

Topics: alpha-Defensins; Bronchiolitis; Cells, Cultured; Cystic Fibrosis; Epithelial Cells; Fibroblasts; Haemophilus Infections; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-8; Lung; Transforming Growth Factor beta; Vascular Endothelial Growth Factors

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