interleukin-8 and Stevens-Johnson-Syndrome

Toxic epidermal necrolysis (TEN) is a fatal cutaneous adverse reaction that occasionally affects multiple organs. Acute respiratory distress syndrome (ARDS) is a rare complication that can cause rapid and potentially fatal pulmonary dysfunction. However, the mechanisms underlying TEN-induced ARDS remain unknown. This retrospective single-center study aimed to identify potential biomarkers for predicting ARDS onset in TEN patients. Pre-treatment serum samples were collected from 16 TEN patients and 16 healthy controls (HCs). The serum levels of cytokines/chemokines were determined using the Luminex Assay Human Premixed Multi-analyte kit. The expression levels of cytokines and chemokines in the skin were examined via immunohistochemistry. The serum levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-6, and IL-8 were significantly higher in TEN patients with ARDS than in those without ARDS and in HCs, whereas those of CCL2 and IL-8 were not significantly different between TEN patients without ARDS and HCs. There was no significant difference in CCL2 and IL-8 expression in the skin between TEN patients with and without ARDS. Interestingly, there were no significant differences in the cytokine/chemokine levels between TEN and other organ damage, other than ARDS and TEN without any organ damage. We further analyzed the changes in cytokine/chemokine levels before and after treatment in two TEN patients with ARDS. CCL2, IL-6, and IL-8 levels decreased after systemic treatment compared to their baseline levels before treatment at an early stage. These results suggest that IL-8 and CCL2 may be involved in the pathogenesis of TEN-induced ARDS and have potential application as predictive markers for ARDS onset.

Topics: Biomarkers; Chemokines; Cytokines; Humans; Interleukin-6; Interleukin-8; Ligands; Respiratory Distress Syndrome; Retrospective Studies; Stevens-Johnson Syndrome

To investigate the role of miRNA in the pathogenesis underlying ocular surface complications in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in the chronic stage. Using oligonucleotide microarrays, we performed comprehensive miRNA analysis of the conjunctival epithelium of SJS/TEN patients with severe ocular complications (SOC) in the chronic stage (n = 3). Conjunctival epithelium of patients with conjunctival chalasis (n = 3) served as the control. We confirmed the down- and up-regulation of miRNA of interest by quantitative real-time polymerase chain reaction (RT-PCR) assays using the conjunctival epithelium from 6 SJS/TEN with SOC patients and 7 controls. We focused on miRNA-455-3p, which is significantly upregulated in the conjunctival epithelium of the SJS/TEN patients, and investigated its function by inhibiting miR-455-3p in primary human conjunctival epithelial cells (PHCjEs). Comprehensive miRNA expression analysis showed that the expression of 5 kinds of miRNA was up-regulated more than fivefold, and that the expression of another 5 kinds of miRNA was down-regulated by less than one-fifth. There was a significant difference between the SJS/TEN patients and the controls [analysis of variance (ANOVA) p < 0.05]. Quantitative miRNA PCR assay showed that hsa-miR-31* and hsa-miR-455-3p were significantly up-regulated in the conjunctival epithelium of the SJS/TEN patients. Comprehensive gene expression analysis of PHCjEs transfected with the hsa-miR-455-3p inhibitor and quantitative RT PCR assay showed that ANKRD1, CXCL8, CXCL2, GEM, PTGS2, RNASE8, IL6, and CXCL1 were down-regulated by the hsa-miR-455-3p inhibitor. Quantitative RT-PCR, focused on the genes that tended to be up-regulated in SJS/TEN with SOC, revealed that the expression of IL1A, KPRP, IL36G, PPP1R3C, and ADM was significantly down-regulated in PHCjEs transfected with the hsa-miR-455-3p inhibitor. Our results suggest that miRNA-455-3p could regulate many genes including innate immune related genes in human conjunctival epithelium, and that its up-regulation contributes to the pathogenesis on the ocular surface in SJS/TEN patients with the SOC in the chronic stage. Our findings may lead to the development of new treatments using the miRNA-455-3p inhibitor.

Topics: Adult; Chemokine CXCL2; Conjunctiva; Epithelium; Humans; Interleukin-8; MicroRNAs; Middle Aged; Muscle Proteins; Nuclear Proteins; Repressor Proteins; Stevens-Johnson Syndrome

This study aimed to clarify predictive biomarkers of mild and severe ocular complications of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by examining the cytokines in tears. In 121 chronic-phase SJS/TEN eyes, cytokines in tear samples collected using Schirmer test strips were measured, and ocular sequelae severity was evaluated using an Ocular Surface Grading Score (OSGS) involving 7 components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening), with findings categorized into grades 0-3 (maximum total OSGS: 21). Changes in cytokines between the mild and severe groups (mild: total OSGS of 10 or less, severe: total OSGS of 11 or more), and changes between SJS/TEN cases with and without each of the 7 components, were compared. In the severe group, there was significant upregulation of interleukin (IL)-8 (P < 0.01) and Granzyme B (GrzB) (P < 0.05). IL-8 was significantly upregulated in eyes with conjunctivalization, neovascularization, or opacification, GrzB was upregulated in eyes with keratinization, interferon-γ-inducible protein 10 (IP-10) was downregulated in eyes with conjunctivalization or neovascularization, and IL-1α was upregulated in eyes with opacification (all: P < 0.05). IL-8 and IP-10 was involved in conjunctivalization and neovascularization, while GrzB was involved in keratinization. IL-8 and GrzB in tears may reflect SJS/TEN-related ocular sequelae severity.

Topics: Adolescent; Adult; Biomarkers; Chemokine CXCL10; Child; Disease Progression; Early Diagnosis; Eye Diseases; Female; Gene Expression Regulation; Granzymes; Humans; Interleukin-1alpha; Interleukin-8; Male; Severity of Illness Index; Stevens-Johnson Syndrome; Tears; Young Adult

Topics: Chemotactic Factors; Chemotaxis, Leukocyte; Humans; Interleukin-8; Neutrophils; Stevens-Johnson Syndrome

To compare the resolution of inflammation and long-term results of cultivated and conventional limbal stem cell transplantation (LSCT) in a patient with Stevens-Johnson syndrome (SJS).. Interventional case report.. A 32-year-old man with SJS and bilateral total limbal stem cell deficiency underwent cultivated LSCT in the right eye, followed by conventional LSCT in the left eye three weeks later. The postoperative medication included dexamethasone 0.1% and ofloxacin 0.3% eyedrops and a tapering dose of systemic corticosteroid, cyclosporine, and cyclophosphamide. Tear samples were collected and analyzed for interleukin (IL) 8 levels.. Complete corneal epithelialization was achieved 48 hours after cultivated LSCT, compared with three weeks after conventional LSCT. Ocular inflammation and IL-8 levels decreased more rapidly in the eye with cultivated LSCT. Four years after surgery, more severe corneal scarring and opacification were noted in the conventional LSCT eye.. Cultivated LSCT resulted in a better clinical result and vision, with less stromal scarring compared with conventional LSCT.

Topics: Adult; Adult Stem Cells; Cells, Cultured; Corneal Diseases; Epithelial Cells; Epithelium, Corneal; Humans; Interleukin-8; Limbus Corneae; Male; Stem Cell Transplantation; Stevens-Johnson Syndrome; Tears

In drug-induced toxic epidermal necrolysis (TEN), the epidermal destruction is associated with a slight to moderate lymphomonocytic cell infiltrate. Interleukin (IL)-8, which is a keratinocyte-derived pro-inflammatory cytokine, might be involved in this process. The IL-8 receptor CXCR2 has also been shown to be overexpressed in some epidermal disorders.. IL-8 concentration was measured by ELISA in both serum and blister fluid from 10 patients with TEN. Data were compared with similar dosages performed in 15 cases of second-degree burn and 7 cases of bullous pemphigoid (BP). CXCR2 expression on keratinocytes was studied using immunohistochemistry on skin biopsies performed in TEN bullous lesions and clinically uninvolved skin of the same patients.. IL-8 was significantly overexpressed in TEN blister fluid compared with TEN serum (P = 0.0015). However, no difference was found in IL-8 concentrations present in blister fluid of TEN, second-degree burn and BP. CXCR2 was moderately expressed in the epidermis of some TEN blisters, but was never expressed in clinically uninvolved skin. CXCR2 expression was not found in the follicular epidermal root sheaths of patients with TEN.. These results indicate that abundant IL-8 appears to be locally produced in TEN epidermis, but this overexpression is not disease-specific. Because of the paucity of the inflammatory infiltrate in TEN, it is unlikely that IL-8 induces epidermal destruction through its chemotactic activity. Moreover, the complete absence of neutrophils in TEN lesions indicates that the major chemotactic effect of IL-8 on neutrophils is not operative in TEN skin. This implies that IL-8 activates different functions according to the local environment. CXCR2 expression on TEN keratinocytes is expressed on some necrotic keratinocytes, consistent with a discrete IL-8 proapoptotic activity. The lack of CXCR2 expression in the follicular root sheaths argues against a role for IL-8 in TEN epidermal repair.

Topics: Adult; Aged; Blister; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Epidermis; Female; Humans; Interleukin-8; Keratinocytes; Male; Middle Aged; Receptors, Interleukin-8B; Stevens-Johnson Syndrome