Differential expression of tear film cytokines in Stevens–Johnson syndrome patients and comparative review of literature

Abstract

To investigate the differential expression of tear cytokine levels among chronic Stevens–Johnson syndrome (SJS) patients to better understand the role of significantly altered cytokines in disease development. Tear samples were collected using Schirmer strips in 24 eyes of chronic SJS, 24 eyes of age and gender-matched controls, and 14 eyes of aqueous deficiency dry eye disease (DED) patients. The cytokine analysis was performed among 18 analytes which include pro-inflammatory, anti-inflammatory factors, and ELR-negative CXC chemokines. String analysis was performed for the significantly altered cytokines to understand their co-expression and role in the disease development. Additionally, a literature review was conducted to identify the signature cytokines present in chronic SJS tears. The differential expression of IL-6 (p ≤ 0.029), CXCL8/IL-8 (p ≤ 0.009), IL-1β (p ≤ 0.041), IL-2 (p ≤ 0.025), IL-10 (p ≤ 0.053), and CXCL-10 (p ≤ 0.044) were observed in chronic SJS patients and healthy controls. Whereas, IL-6 (p ≤ 0.029), CXCL8/IL-8 (p ≤ 0.058), CCL4 (p ≤ 0.056), GM-CSF (p ≤ 0.0001) IL-10 (p ≤ 0.025), and CXCL-10 (p ≤ 0.010), were differentially expressed in SJS as compared to severe DED patients. String analysis of the significantly altered cytokines revealed the involvement of several biological processes including the chronic inflammatory response, nitric oxide synthesis, angiogenesis, and cellular response to drugs. Among all the cytokines evaluated, the expression of CXCL8/IL-8 and CXCL10 levels were consistently reported in the literature. There was a differential expression of tear cytokines in SJS when compared to DED and healthy controls. The differential expression of CXCL8/IL-8 and CXCL10 was in line with existing literature and their role in chronic SJS pathogenesis merits further evaluation.

Ocular surface involvement and histopathologic changes in the acute stage of Stevens- Johnson Syndrome and Toxic Epidermal Necrolysis: a cross-sectional study

“…Similar to a previous case report [15], our study also found that IL-6 and IL-8 in SJS/TEN patients in the acute phase were signi cantly upregulated. However, unlike the decreased expression of IL-10, TNF-α, and IL-12 in chronic SJS/TEN [11,14], our research showed an increase of such cytokines in the acute disease phase. Even if patients already receive active systemic glucocorticoid and immune globulin therapy, their ocular surface still suffers from a cytokine storm, which represents the organs and tissues that produce tears and palpebral sebum, containing lacrimal glands, accessory lacrimal glands, meibomian glands, ocular surface epithelial cells, and conjunctival goblet cells, all experience a strong immune attack at the very early stage of diseases or even before the onset of ocular symptoms and signs.…”

“…However, no research has yet assessed the ocular surface of acute SJS/TEN patients using conjunctival impression cytology.The pathogenesis of SJS/TEN is not completely clear; it is considered to be a T-cell mediated, delayed hypersensitivity activity, and cytokines play an important role in the development and progression of these diseases [7, 8]. The dynamics of multiple cytokines in the different stages of SJS/TEN were observed in epidermal lesions, blister uid, serum, corneal epithelium, and tears [9][10][11]. As a noninvasive method, tear multi-cytokine analysis helps make an accurate and quantitative assessment of ocular surface in ammation.…”

“…As a noninvasive method, tear multi-cytokine analysis helps make an accurate and quantitative assessment of ocular surface in ammation. Several studies have focused on the pathophysiological mechanism of ocular surface in ammation in chronic SJS/TEN patients through tear cytokine detection [11][12][13][14]. However, the study of tear cytokine analysis for patients with acute SJS/TEN is lacking, except for one case report that monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) were rapidly increased in an SJS patient's tears at the acute stage [15].…”

Ocular Surface Inflammatory Disorders (OSID): A Collective of Systemic Etiologies Which Cause or Amplify Dry Eye Syndrome

“…The evidence for inflammation is also noticeable through tear film proinflammatory cytokine detection which revealed an increased detection of Interleukin (IL)-1, IL-6, and IL-8 in dry eye patients ( 14 , 15 ). Interestingly in diverse OSID, similar mechanisms of disease and results have been demonstrated, such as presence of these cytokines in tear film of ocular GVHD patients ( 16 ), SJS ( 17 ) and ocular cicatricial pemphigoid (OCP) ( 18 ) compared to normal controls. Data for positive presence of inflammation on these conditions is likewise observable in impression cytology of bulbar and tarsal conjunctiva ( 19 ) and through in vivo confocal imaging of the ocular surface ( 20 ).…”

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Qiju Dihuang Pill against Dry Eye Disease

“…Computational and Mathematical Methods in Medicine DED. The proinflammatory factors associated with DED that have been identified in the study are TNFα and IL-1, and CXCL8 is highly expressed in the eyes of patients with chronic dry syndrome [37,38]. MAPK is an important inflammatory target.…”