Elevated cytokine levels in vitreous as biomarkers of disease severity in infectious endophthalmitis

• Published in: PloS one 2018-10, Vol.13 (10), p.e0205292-e0205292
• Main Authors: Deshmukh, Dhanshree, Chakrabarti, Moumita, Jayasudha, Rajagopalaboopathi, Hasnat Ali, Mohammed, Tyagi, Mudit, Sharma, Savitri, Joseph, Joveeta
• Format: Article
• Language: English
• Subjects: Acuity; Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics; Bacterial Infections - diagnosis; Bacterial Infections - immunology; Bacterial Infections - metabolism; Bacterial Infections - pathology; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Care and treatment; Cataracts; Chemokine CXCL1 - genetics; Chemokine CXCL1 - immunology; Chemokines; Child; Child, Preschool; Correlation; Culture; Cytokines; Diabetes mellitus; Diabetic retinopathy; Diabetic Retinopathy - diagnosis; Diabetic Retinopathy - immunology; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Diagnosis; Empirical analysis; Endophthalmitis; Endophthalmitis - diagnosis; Endophthalmitis - immunology; Endophthalmitis - metabolism; Endophthalmitis - pathology; Epidemiology; Female; Gene Expression; Genetic aspects; Gram-Negative Bacteria - isolation & purification; Gram-Positive Bacteria - isolation & purification; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - genetics; Granulocyte Colony-Stimulating Factor - immunology; Growth factors; Health aspects; Humans; IL-1β; Immunoassay; Immunopathogenesis; Infections; Infectious diseases; Inflammation; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin 1 Receptor Antagonist Protein - genetics; Interleukin 1 Receptor Antagonist Protein - immunology; Interleukin 1 receptors; Interleukin 6; Interleukin 8; Interleukin-6 - genetics; Interleukin-6 - immunology; Interleukin-8 - genetics; Interleukin-8 - immunology; IP-10 protein; Male; Medical diagnosis; Medicine and Health Sciences; Microbiology; Middle Aged; Monocyte chemoattractant protein 1; Pathogenesis; Patients; Prospective Studies; Retina; Retinal Detachment - diagnosis; Retinal Detachment - immunology; Retinal Detachment - metabolism; Retinal Detachment - pathology; Retinopathy; Severity of Illness Index; Social Sciences; Therapy; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Visual Acuity; Vitreous Body - immunology; Vitreous Body - metabolism; Vitreous Body - pathology; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0205292

To investigate the immunopathogenesis of endophthalmitis, and determine if cytokine profiles could serve as biomarkers of disease severity in infectious endophthalmitis. Vitreous samples of 46 patients clinically diagnosed as endophthalmitis (of which 25 were culture positive) and 20 non-infectious controls from patients with Retinal Detachment (RD) or diabetic retinopathy were included in the study. The cytokine and chemokine expression patterns of 40 immune mediators including 6 antiinflammatory cytokines, 15 proinflammatory cytokines, 9 Growth factors and 10 proinflammatory chemokines in the vitreous were were analyzed by multiplex cytokine immunoassay. In addition, significant immune mediators were correlated with initial and final visual acuity (VA). Our results demonstrated elevated expression of 16 mediators such as GCSF, GRO, IFN-γ, IL-1α, IL-1β, IL-1 RA, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIP-1α, IL-1β, TGF-α, TNF-α in patients with culture positive endophthalmitis. Cytokine profile expression significantly differed between patients with proven endophthalmitis and the non-infectious controls in heat map analysis. PCoA plot indicated five mediators (IL-1RA, IL-6, IL-8, GRO, G-CSF) as biomarkers that could be Independent Predictors of Disease especially in culture negative cases. Correlation of cytokines with VA revealed strong association between the initial VA and intraocular levels of TGF-α, IL-1β and IL-8 but there was no correlation with the severity or visual outcome of infection. In comparison to non-infectious ocular conditions, the pathogenesis of infectious endophthalmitis correlates with increased expression levels of IL-1RA, IL-6, IL-8, GRO, G-CSF. Understanding cytokine profiles in culture negative endophthalmitis patients could aid in therapy in non-responders to empirical antibiotic therapy.