Cytokine concentrations in bronchoalveolar lavage fluid of patients with systemic sclerosis

Bolster, Marcy B.; Ludwicka, A; Sutherland, Susan E.; Strange, Charlie; Silver, Richard M.

doi:10.1002/art.1780400422

Cited by 125 publications

(68 citation statements)

References 41 publications

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“…The patients with untreated alveolitis also had a significantly higher mortality rate. The presence of inflammatory cells in the BAL (Ն3% PMNs) also correlated with intrapulmonary accumulation of inflammatory cytokines and chemokines (20,21), especially interleukin-8 and macrophage inhibitory protein ␣. We investigated the cumulative distribution of our data and were not able to find a naturally occurring "cut point" above or below which there was a division supporting alveolitis or no alveolitis.…”

Section: Discussionmentioning

confidence: 90%

Regional differences in bronchoalveolar lavage and thoracic high‐resolution computed tomography results in dyspneic patients with systemic sclerosis

Clements

Goldin

Kleerup

et al. 2004

Arthritis & Rheumatism

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Objective. Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc).Although early identification and treatment of alveolitis may prevent deterioration of lung function, the best approach for diagnosing active alveolitis remains controversial. This study was undertaken to investigate the utility of high-resolution computed tomography (HRCT) of the chest, in comparison with bronchoalveolar lavage (BAL), in the diagnosis of alveolitis in these patients.Methods. Eighteen patients with SSc and dyspnea were evaluated for ILD by pulmonary function testing and bronchoalveolar lavage (BAL), and 15 of these patients underwent chest HRCT. BAL was performed in either the middle lobe or the lingula, and also in a lower lung segment. Differential cell counts were determined by clinical cytopathology, with retrospective recounting in a blinded manner by a single technician. Active alveolitis was defined as the presence of >3.0% polymorphonuclear cells and/or >2% eosinophils in BAL fluid. BAL fluids were cultured for bacteria, mycobacteria, and fungi. HRCT scans were evaluated in a blinded manner for ground-glass opacification and fibrosis in the lavaged lobes.Results. Nine of the 18 patients had active alveolitis recorded in both lavaged segments, while in 4 patients it was recorded in only 1 segment (lower lobe in 3). Following repeat differential cell counting, 3 patients were reclassified as having active alveolitis and 1 as having no alveolitis. Culture of BAL fluid identified clinically unsuspected infection in 3 patients. For the right middle lung lobe or lingula there was excellent agreement between ground-glass opacification and the finding of alveolitis on BAL from segments in the same lung regions, but this was not observed for the lower lobes. The correlation between fibrosis on HRCT and the presence of alveolitis on BAL was significant for the lower lobes but not the middle lung fields.Conclusion. BAL of the middle lobe or lingula may underestimate the presence of active alveolitis. Similarly, while ground-glass opacification on HRCT accurately predicted alveolitis in the middle lung fields, HRCT did not detect all sites of inflammation and did not identify infectious etiologies. These data suggest that, in addition to HRCT, BAL with lavage, differential cell counting, and culture from at least 2 segments of lung be performed for diagnosing SSc alveolitis.

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Section: Discussionmentioning

confidence: 90%

Regional differences in bronchoalveolar lavage and thoracic high‐resolution computed tomography results in dyspneic patients with systemic sclerosis

Clements

Goldin

Kleerup

et al. 2004

Arthritis & Rheumatism

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“…Increased levels of CXCL8 protein have been observed in SSc skin biopsy specimens (28) and in bronchoalveolar lavage fluid from patients with SSc (29). Scleroderma fibroblasts cultured in vitro were found to produce more CXCL8 than that in normal fibroblasts (30).…”

Section: Discussionmentioning

confidence: 99%

Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Lee¹,

Zhao²,

Kim³

et al. 2007

Arthritis & Rheumatism

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Objective. To examine genetic polymorphisms in the chemokine pathway, and to assess their interactions in relation to susceptibility to systemic sclerosis (SSc).Methods. To identify the risk of SSc conferred by genetic polymorphisms in the chemokine pathway, 10 single-nucleotide polymorphisms (SNPs) from 8 candidate genes were studied in 99 patients with SSc and 198 age-and sex-matched controls in a Korean population. SNPs were genotyped by polymerase chain reactionrestriction fragment length polymorphism or sequencespecific primer methods. Genetic associations between each SNP and SSc risk, calculated as odds ratios with 95% confidence intervals, were estimated using chisquare tests. Haplotypes for the 2 polymorphisms in the gene CCL5 (RANTES) were constructed, and their associations with SSc were tested. Gene-gene interactions were investigated using a recently described novel method, and the results were confirmed by conditional logistic regression. Adjustment for multiple testing was based on Bonferroni correction.Results. There was significant evidence of genegene interaction between polymorphisms in the genes CXCL8 (interleukin-8) and CCL5, and both of these were associated with an increased risk of SSc. This SNP-SNP interaction was confirmed by 2 independent statistical methods. The associations remained significant after Bonferroni adjustment for multiple testing. No significant association between each individual SNP or haplotype and the risk of SSc was found.Conclusion. Crosstalk between the 2 chemokines CXCL8 and CCL5 may contribute to the susceptibility to SSc.

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“…A recent study has shown that levels of MIP-1a are significantly elevated in BAL fluid of SSc patients with alveolitis when compared with those of SSc patients without alveolitis or normal controls [20]. In addition, enhanced MIP-1a expression has been reported in alveolar and interstitial macrophages, and interstitial fibroblasts of patients with ILD [13].…”

Section: Discussionmentioning

confidence: 99%

Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and MIP-1β) in patients with systemic sclerosis: MCP-1 and MIP-1α may be involved in the development of pulmonary fibrosis

Hasegawa

Sato

Takehara

1999

Clinical and Experimental Immunology

196

126

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SUMMARYTo determine the role of chemokines in the pathogenesis of systemic sclerosis (SSc), we examined serum levels, spontaneous production by peripheral blood mononuclear cells (PBMC), and histological distribution in the affected skin, of MCP-1, MIP-1a and MIP-1b in SSc patients. Serum levels of these chemokines were examined by ELISA in 58 patients with SSc and 20 normal controls. The levels of these chemokines in culture supernatants from PBMC were also measured by ELISA. Serum levels and spontaneous production levels by PBMC of MCP-1, MIP-1a, and MIP-1b were significantly elevated in patients with SSc compared with normal controls. Elevated serum levels of MCP-1 and MIP-1a significantly correlated with the presence of pulmonary fibrosis. MCP-1 expression in the skin of SSc was immunohistochemically examined using anti-MCP-1 MoAb. MCP-1 was strongly expressed in the epidermis, inflammatory mononuclear cells, and vascular endothelial cells in the sclerotic skin of SSc patients, but not expressed in any control skin. Furthermore, the MCP-1 expression in inflammatory mononuclear cells and endothelial cells significantly correlated with earlier onset of SSc. Thus, MCP-1, MIP-1a and MIP-1b may be involved in the disease process, possibly by augmenting leucocyte migration into the affected tissues in SSc. Furthermore, MCP-1 and MIP-1a may play an important role in the development of pulmonary fibrosis in SSc.

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Cytokine concentrations in bronchoalveolar lavage fluid of patients with systemic sclerosis

Cited by 125 publications

References 41 publications

Regional differences in bronchoalveolar lavage and thoracic high‐resolution computed tomography results in dyspneic patients with systemic sclerosis

Regional differences in bronchoalveolar lavage and thoracic high‐resolution computed tomography results in dyspneic patients with systemic sclerosis

Evidence of potential interaction of chemokine genes in susceptibility to systemic sclerosis

Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and MIP-1β) in patients with systemic sclerosis: MCP-1 and MIP-1α may be involved in the development of pulmonary fibrosis

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