Exhaled IL-8 in Systemic Lupus Erythematosus with and without Pulmonary Fibrosis

Abstract

The purpose of this study is to evaluate the relationship between the concentration of interleukin-8 (IL-8) in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALF) with the disease activity score and pulmonary function of systemic lupus erythematosus (SLE) patients with and without pulmonary fibrosis. Thirty-four SLE patients and 31 healthy controls were enrolled and evaluated using high-resolution computed tomography (HRCT), pulmonary function tests, systemic lupus activity measure (SLAM), assessing BALF and EBC. IL-8 levels in BALF and EBC samples were measured with an enzyme-immunosorbent assay kit. The mean (±SEM) IL-8 concentrations in BALF and EBC were higher in SLE patients compared to healthy controls (34.84 ± 95.0 vs. 7.65 ± 21.22 pg/ml, p < 0.001; 3.82 ± 0.52 pg/m vs. 1.7 ± 1.7 pg/ml, p < 0.001, respectively). SLE patients had increased percentage of neutrophils in BALF when compared with control group (1.00 ± 5.99 vs. 0.00 ± 0.56 %, p = 0.0003). Pulmonary fibrosis in HRCT was found in 50 % of SLE patients. The disease activity scored by SLAM was significantly higher and total lung capacity was significantly lower in SLE patients with pulmonary fibrosis (8.00 ± 3.17 vs. 6.00 ± 2.31, p = 0.01; 88.00 ± 28.29 vs. 112.00 ± 21.08 % predicted, p = 0.01, respectively). In SLE patients with pulmonary fibrosis, correlations were found between SLAM and IL-8 concentration in BALF, forced expiratory volume in 1 s and forced vital capacity (r = 0.65, p = 0.006; r = −0.53, p = 0.035; r = −0.67, p = 0.006, respectively). Our results indicate that IL-8 plays an important role in the pathogenesis of SLE. An increased concentration of IL-8 according to BALF could be considered as a useful biomarker of SLE activity and pulmonary fibrosis in SLE.

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

“…For both CD163 + DC3 subsets, the secretomes further regrouped based on disease status, with subclusters comprising only secretomes obtained by culturing with active and inactive SLE (CD163 + CD14 À DC3s) and only active SLE (inflammatory CD163 + CD14 + DC3s) serum ( Figure 7C). Compared to cultures with serum from healthy subjects, only the two CD163 + DC3 subsets significantly increased their secretory capacity when cultured with active SLE serum, especially inflammatory CD163 + CD14 + DC3s, which secreted more pro-inflammatory mediators known to participate in SLE physiopathology, such as BAFF, IL-1a, GRO-a (CXCL1), MCP-3 (CCL7), MIG (CXCL9), SDF-1 (CXCL12), IL-8, VEGF-A, and TWEAK (Kuryliszyn-Moskal et al, 2007;Li et al, 2008;Liao et al, 2016;Nielepkowicz-Go zdzi nska et al, 2014;Parks et al, 2004;Samy et al, 2017;Sun et al, 2018) (Figures 7D, 7E, and S7D). These data reaffirm that cDC2s should not be studied as a whole, because when exposed to a pathologic environment (e.g., serum from SLE patients), cDC2 subsets show striking functional differences in their responses: both CD163 + DC3 subsets, and particularly inflammatory CD163 + CD14 + DC3s, show a specific and strong pro-inflammatory response.…”

Exhaled Breath Condensate: Technical and Diagnostic Aspects

“…Nielepkowicz-Goździńska et al detected significantly increased IL-8 [ 220 ], IL-6, and IL-10 [ 221 ], both in EBC and in BAL of SLE patients. Furthermore, the abovementioned changes were significantly correlated with the disease activity [ 222 ].…”

CXCL13, CCL4, and sTNFR as circulating inflammatory cytokine markers in primary and SLE-related autoimmune hemolytic anemia

“…Therefore, elevated level of circulating CCL4 instead of CCL3 among AIHA patients might indicate a boost in their erythroid proliferation and reticulocytosis. On the other hand, CCL2 and CXCL8, both capable of inducing respiratory burst as well as being chemoattractants, had been under intensive investigation among SLE patients [ 11 - 18 ]. Although both cytokines were argued to be elevated in the scenario of SLE, CCL2 was regarded as an important biomarker for lupus nephritis flair [ 13 - 16 ], and CXCL8 for lupus associated interstitial lung diseases [ 17 , 18 ].…”

“…On the other hand, CCL2 and CXCL8, both capable of inducing respiratory burst as well as being chemoattractants, had been under intensive investigation among SLE patients [ 11 - 18 ]. Although both cytokines were argued to be elevated in the scenario of SLE, CCL2 was regarded as an important biomarker for lupus nephritis flair [ 13 - 16 ], and CXCL8 for lupus associated interstitial lung diseases [ 17 , 18 ]. In immune-mediated hemolytic anemia canine models, CCL2 was also argued to experience marked up-regulation and to demonstrate prognostic value [ 19 ].…”