interleukin-8 and Sarcoidosis

Oxidative stress and low antioxidant levels are implicated in the aetiology of sarcoidosis, an inflammatory disease. Quercetin is a potent dietary antioxidant that also displays anti-inflammatory activities. Consequently, the aim is to examine the effect of quercetin supplementation on markers of oxidative stress and inflammation in sarcoidosis.. A double-blind intervention study has been conducted with two groups of non-smoking, un-treated sarcoidosis patients, matched for age and gender. One group was given 4x500 mg quercetin (n = 12) orally within 24 h, the other one placebo (n = 6). Plasma malondialdehyde levels were used as marker of oxidative damage, plasma ratios of TNFα/IL-10 and IL-8/IL-10 as pro-inflammatory markers.. Quercetin supplementation improved the antioxidant defence, indicated by the increased total plasma antioxidant capacity. Moreover, quercetin supplementation also reduced markers of oxidative stress and inflammation in the blood of sarcoidosis patients. The effects of quercetin supplementation appeared to be more pronounced when the levels of the oxidative stress and inflammation markers were higher at baseline.. Sarcoidosis patients might benefit from the use of antioxidants, such as quercetin, to reduce the occurring oxidative stress as well as inflammation. The effects of long-term use of antioxidant supplementation in sarcoidosis, using e.g. quercetin, on improvement of lung function remain to be investigated. (www.clinicaltrials.gov; NCT-00402623).

Topics: Adult; Aged; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Interleukin-10; Interleukin-8; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Quercetin; Sarcoidosis; Tumor Necrosis Factor-alpha

A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU).. Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included.. Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal-Wallis test, the Mann-Whitney or Fisher test and the Principal Component Analysis (PCA).. IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS.. The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).

Topics: Aqueous Humor; Chemokine CXCL10; Cross-Sectional Studies; Cytokines; Humans; Interleukin-8; Sarcoidosis; Tuberculosis, Ocular; Uveitis

The objective was to study both ex vivo and in vitro secretion of pro-inflammatory cytokines in patients affected by Blau syndrome (BS) and carrying p.E383K mutation in the CARD15/NOD2 gene associated with the disease. For ex vivo studies, peripheral blood mononuclear cells (PBMCs), serum from three patients and healthy controls have been collected. PBMCs have been cultured in the presence or absence of inflammatory enhancers, such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP). The levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were assayed by either immunoassay or array-based system. For in vitro studies, different constructs were created cloning human wild-type and p.E383K-mutated NOD2 cDNA into the expression vector pCMV-Tag2c. HEK293 cell lines were stably transfected, cultured with or without MDP and IL-8 level was assayed in their surnatants. Statistical analysis in both studies was performed using non-parametric tests. Both ex vivo and in vitro studies have not identified a significant increase in secretion of the analyzed proinflammatory cytokines. p.E383K-mutated NOD2 transfected cells express low level of IL-8. The ex vivo basal level results from both serum and PBMCs surnatants present similar levels of IL-1β, IL-6, TNF-α and IFN-γ in patients and controls. The presence of the stimulant agents (LPS and MDP), either individual or paired, does not lead to significant increases in all cytokines concentrations in patients compared to controls. Taken together, the ex vivo and in vitro data suggest that there is not a primary mediation of IL-1β and other pro-inflammatory cytokines in BS patients carrying p.E383K.

Topics: Adult; Arthritis; Biomarkers; Case-Control Studies; Cytokines; Extremities; Fathers; Female; Humans; In Vitro Techniques; Interferon-gamma; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Mutation; Nod2 Signaling Adaptor Protein; Nuclear Family; Pedigree; Sarcoidosis; Synovitis; Tumor Necrosis Factor-alpha; Uveitis

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

Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins.. We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (nongranulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in nongranulomatous myocarditis had no effect, even at much higher concentrations. We also observed myocardial expression of IL-17 and TNF-α and elevated levels of serum inflammatory mediators, including IL-6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β, in patients with ARVC (all P<0.0001 compared with controls).. The results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

Topics: Adolescent; Adult; Aged; Animals; Arrhythmias, Cardiac; Autopsy; Biopsy; Cardiomyopathies; Case-Control Studies; Cells, Cultured; Chemokine CCL2; Chemokine CCL4; Child; Desmosomes; Female; gamma Catenin; Humans; Intercellular Junctions; Interleukin-17; Interleukin-6; Interleukin-8; Male; Middle Aged; Models, Animal; Myocarditis; Myocytes, Cardiac; Rats; Rats, Wistar; Sarcoidosis; Signal Transduction; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Right; Young Adult

Enhanced production of reactive oxygen species (ROS), capable of reducing endogenous defense levels and enhancing inflammation, is suggested to play a role in sarcoidosis. Antioxidant supplementation might offer protection against such ROS-mediated damage. A promising candidate for antioxidant supplementation is the flavonoid quercetin.. To determine the antioxidant and inflammatory status in sarcoidosis. Furthermore, the potential of quercetin to mitigate the occurring inflammation will be assessed.. Non-smoking sarcoidosis patients and healthy controls matched for age, gender and dietary behavior were enrolled (NCT-00512967). Measurements included assessment of total plasma antioxidant capacity, vitamin C, uric acid, glutathione, basal and LPS-induced levels of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-8 and -10 as well as the effect of quercetin on these levels.. Compared to their controls, the sarcoidosis patients displayed significantly lower total plasma antioxidant capacity, decreased levels of vitamin C, uric acid and glutathione and increased levels of basal TNFalpha and IL-8. Quercetin significantly decreased ex vivo LPS-induced TNFalpha- and IL-8 production in a concentration-dependent manner in both groups. Interestingly, this quercetin effect was more pronounced in sarcoidosis patients.. The endogenous antioxidant defense was significantly reduced in sarcoidosis, indicating that oxidative stress underlies the pathology of this disease. Furthermore, the inflammatory status was significantly enhanced in sarcoidosis. Finally, our results regarding the effect of quercetin on cytokine production imply that sarcoidosis patients might benefit from antioxidant supplementation not only by empowering the relatively low protection against ROS but also by reducing inflammation.

Topics: Adult; Antioxidants; Ascorbic Acid; Biomarkers; Case-Control Studies; Chromans; Dose-Response Relationship, Drug; Female; Flavonoids; Glutathione; Humans; Interleukin-10; Interleukin-8; Lipopolysaccharides; Lung; Male; Middle Aged; Oxidative Stress; Quercetin; Sarcoidosis; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Uric Acid

Sarcoidosis (SAR) is a systemic granulomatous inflammatory disease characterized by recruitment and activation of peripheral blood mononuclear cells to the sites of disease. Neovascularisation is a principal vascular response in chronic inflammation and hypoxia. The aim of the study was to evaluate the effect of sera from sarcoidosis patients on angiogenic capability of different subsets of normal peripheral human mononuclear cells (MNC) in relation to IL-6 and IL-8 serum levels, to radiological stages of disease and to the presence of extrapulmonary changes. Serum samples obtained from 42 sarcoidosis patients were examined. There were 12 patients in stage I, 16 patients in stage II, and 14 in stage III. In order to quantify angiogenesis, a leukocyte-induced angiogenesis assay was performed by a method of Sidky and Auerbach. MNC were depleted in monocytes by glass adherence and phagocytosis of iron particles techniques. IL-6 and IL-8 in sera from sarcoidosis patients were evaluated by an ELISA-based assay. Sera from sarcoidosis patients enhanced angiogenic capability of normal MNC significantly stronger than sera from healthy donors (P<0.001). Angiogenic activity of sera in sarcoidosis depended on the stage of disease and appeared most pronounced in stage II (P<0.05). Sera from patients with extrapulmonary changes exerted stronger effect on angiogenesis than sera from patients with thoracic changes only (P<0.001). IL-6 and IL-8 serum level correlated with each other, but no correlation was found between IL-6 and IL-8 serum level and angiogenic activity of the examined sera. Removal of monocytes from MNC eliminated the effect of sera from sarcoidosis patients on angiogenesis compared with the effect of these sera on intact MNC (P<0.001). Sera from sarcoidosis patients and from healthy people constitute a source of mediators participating in angiogenesis. Sera from sarcoidosis patients prime monocytes for production of proangiogenic factors.

Topics: Adult; Aged; Animals; Cough; Dyspnea; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Lymphocyte Subsets; Male; Mice; Mice, Inbred BALB C; Middle Aged; Monocytes; Neovascularization, Pathologic; Radiography; Sarcoidosis; Smoking

IL-15 is a T(H)1-related cytokine that shares many biologic activities with IL-2. Both cytokines bind a specific alpha subunit, and they share the same beta and gamma common receptor subunits for signal transduction. IL-15 has recently been shown to be upregulated in T cell-mediated inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. However, the role and expression of IL-15 in inflammatory lung disease has not been investigated.. In the present study we have evaluated the expression of IL-15 mRNA and protein in bronchial biopsy specimens obtained from patients with sarcoidosis (n = 8), tuberculosis (n = 7), chronic bronchitis (n = 10), and bronchial asthma (n = 8) and compared its expression with that seen in normal control subjects (n = 11).. In situ hybridization and immunocytochemistry were used to detect the number of cells expressing IL-15 mRNA and protein, respectively, within sections of bronchial tissues from all subject groups. In addition, double immunocytochemistry was used to characterize the cellular source of IL-15.. The number of IL-15(+) cells was significantly higher within tissue from patients with sarcoidosis, tuberculosis, and chronic bronchitis compared with that in asthmatic patients and normal control subjects. Similar results were obtained for IL-15 immunoreactivity by using immunohistochemistry. Furthermore, double immunostaining revealed that neutrophils and macrophages are the major source of IL-15.. These results suggest that the expression of IL-15 may be associated with T(H)1-mediated chronic inflammatory diseases of the lung.

Topics: Asthma; Bronchitis; Humans; Immunohistochemistry; Interleukin-15; Interleukin-8; Neutrophils; RNA, Messenger; Sarcoidosis; Th1 Cells; Tuberculosis, Pulmonary

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

There is increasing evidence that the proinflammatory chemokines interleukin-8 (IL-8) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are involved in the pathogenesis of interstitial lung diseases.. We investigated the release of TNF-alpha, IL-8, MIP-1 alpha by cultured bronchoalveolar lavage (BAL) immune cells of patients with idiopathic pulmonary fibrosis (IPF, n = 24), sarcoidosis (SAR, n = 24), and controls (n = 20) by ELISA. Furthermore, mRNA expression of these cytokines in BAL cells immediately frozen after bronchoscopy was determined. The clinical course of the disease was evaluated and the patients were subdivided into groups with progressing or stable disease.. TNF-alpha, IL-8, and MIP-1 alpha were significantly elevated in the supernatants of BAL immune cells of IPF and SAR patients with progressing disease compared to controls (p < 0.005 in both diseases) and also when compared to patients with stable disease (IPF p < 0.005, SAR p < 0.05). Interestingly, the release of TNF-alpha, IL-8, and MIP-1 alpha did not differ significantly between IPF patients with stable disease and controls, whereas in SAR patients with stable disease a difference at a low significance level (p < 0.05) was obtained. In IPF and SAR patients with progressing disease, a clear mRNA signal of TNF-alpha, IL-8, and MIP-1 alpha was detected in BAL immune cells not having been stimulated by adherence to plastic, whereas in patients with stable disease or controls only a weak signal was observed. MIP-1 alpha release correlated positively with percentage of BAL eosinophils in IPF and SAR. Furthermore, the percentage of eosinophils in BAL was significantly elevated in the IPF subgroup with progressing disease.. Our data demonstrate that an exaggerated expression of TNF-alpha, IL-8, and MIP-1 alpha in BAL immune cells is characteristic for IPF and SAR patients who show progressing disease.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Chemokine CCL4; Chemokines; Humans; Interleukin-8; Macrophage Inflammatory Proteins; Middle Aged; Pulmonary Fibrosis; RNA, Messenger; Sarcoidosis; 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

To find a laboratory indicator for systemic involvement in intermediate uveitis.. Interleukin 8 (IL-8) and C reactive protein (CRP) serum levels were measured in patients with idiopathic intermediate uveitis (n = 61), uveitis controls (n = 143), and normal controls (n = 29). The records of those with intermediate uveitis were reviewed with the emphasis on disease activity and severity as characterised by the presence of cystoid macular oedema, vitreous exudates or snowbank formation, papillitis, and periphlebitis.. Increased serum IL-8 (> or = 20 pg/ml) was found in 27 out of 61 patients with intermediate uveitis (p < 0.01), 12 of 27 patients with sarcoid uveitis (p < 0.05), in 19 of 30 patients with HLA-B27 associated acute anterior uveitis (p < 0.05), and in five of 29 healthy controls. Raised IL-8 levels in intermediate uveitis were significantly associated with active disease (p < 0.001) and the presence of vitreous exudates (p < 0.001), papillitis, and periphlebitis (p < 0.01). Elevated CRP levels were found in 12 of the 143 uveitis controls but in none of the intermediate uveitis patients or normal controls. During follow up an associated systemic disease was more frequently noticed in patients with an elevated serum IL-8 at entry into the study.. Elevated IL-8 serum levels were found in patients with active intermediate uveitis of unknown origin. An elevated IL-8 level seems to predispose the patient to a later development of associated systemic disease.

Topics: Adult; Biomarkers; C-Reactive Protein; Female; Follow-Up Studies; HLA-B27 Antigen; Humans; Interleukin-8; Male; Middle Aged; Sarcoidosis; Severity of Illness Index; Uveitis, Anterior; Uveitis, Intermediate

A variety of cytokines have been implicated in the pathogenesis of pulmonary sarcoidosis, but the exact roles of IL-6 and IL-8 are not yet clear. We studied these cytokine levels in BALF from patients with pulmonary sarcoidosis, idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial lung disease and control subjects. IL-6 and IL-8 levels were significantly elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with control subjects. Subjects with sarcoidosis had significantly increased levels of both cytokines compared with controls when the cytokine values were corrected by the total albumin content and the two cytokine levels correlated with each other (r = 0.876). BALF IL-6 levels correlated with percent lymphocytes and percent CD3+ cells. Moreover, when sarcoidosis patients were divided into three groups, those who needed steroid therapy or had progressive disease showed increased cytokine levels in BALF over stable or improved patients. These observations suggest that locally derived IL-6 and IL-8 were increased in sarcoidosis and correlated with activity of this granulomatous lung disease.

Topics: Adult; Biomarkers; Bronchoalveolar Lavage Fluid; Female; Humans; Interleukin-6; Interleukin-8; Macrophages; Male; Sarcoidosis

We determined the serum concentration of interleukin-8 (IL-8) in patients with chronic sarcoidosis and assessed its value as a marker of disease activity. The serum concentrations of IL-8 and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme-linked immunosorbent assays. Serum angiotensin-converting enzyme (ACE) activity was measured by a colorimetric assay in 16 patients with chronic sarcoidosis. Thirteen of the 16 patients with chronic sarcoidosis showed a serum IL-8 concentration higher than the normal range. The mean (+/- S. E.) serum IL-8 concentration in patients with active sarcoidosis (n = 6) was 18.7 +/- 1.3 pg/mL and that in patients with inactive sarcoidosis (n = 10) was 8.0 +/- 1.1 pg/mL; the difference was statistically significant (p = 0.002). An overall positive correlation between serum IL-8 concentration and serum ACE activity was apparent; however, only four of the 16 patients with sarcoidosis had a serum ACE activity greater than the normal range. TNF-alpha was detected in the serum of only two patients. The serum concentration of IL-8 may prove a useful marker for monitoring disease activity in sarcoidosis, especially in the chronic stage.

Topics: Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Osmolar Concentration; Peptidyl-Dipeptidase A; Sarcoidosis; Tumor Necrosis Factor-alpha

Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (Interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN). Increased expression of IL-8 has been described in other inflammatory disorders characterized by neutrophilic infiltration, including psoriasis, rheumatoid arthritis, and the sepsis syndrome, but no studies have assessed this cytokine in the context of interstitial pulmonary disorders. We have previously shown that normal human AM release IL-8 upon appropriate stimulation, but data assessing the expression of IL-8 by human AM in specific pulmonary disease states are lacking. In this study, we examined the expression of steady-state mRNA for IL-8 by human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis and from healthy volunteers. Because it is known that adherence to plastic culture plates may up-regulate gene expression for IL-8 in the absence of additional stimulation, we extracted mRNA immediately from the cell pellet obtained by BAL rather than using cultured alveolar macrophage monolayers. Northern blot analysis was performed to determine IL-8 mRNA expression. We found that BAL cells from patients with IPF constitutively expressed mRNA for IL-8, and the amount of IL-8 mRNA (as assessed by laser densitometry) correlated with the percent of neutrophils on BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Bronchoalveolar Lavage Fluid; Female; Gene Expression; Humans; Interleukin-8; Lung Diseases; Macrophages, Alveolar; Male; Middle Aged; Neutrophils; Pulmonary Fibrosis; RNA, Messenger; Sarcoidosis