Premium
Systemic IL ‐1 β production as a consequence of corneal HSV ‐1 infection – contribution to the development of Herpes Simplex Keratitis
Author(s) -
Murphy C.,
de Chaumont C.,
Shahnazaryan D.,
Malone C.,
Jefferies C.,
Smith S.,
Ni Gabhann J.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0462
Subject(s) - immunology , cytokine , keratitis , medicine , herpes simplex virus , chemokine , pathogenesis , irf3 , western blot , inflammation , biology , virus , immune system , innate immune system , ophthalmology , biochemistry , gene
Purpose Herpes Simplex Virus type‐1 ( HSV ‐1) infection can result in keratitis, a sight‐threatening disease that is the leading cause of infectious corneal blindness in the western world. HSV ‐1 can invade the cornea and remain latent after treatment in the trigeminal ganglia. The pathogenesis of HSK involves a complex interaction between cytokines, chemokines and growth factors, either brought in by inflammatory cells or produced locally. Avoidance of these innate anti‐viral responses can cause lifelong recurrent infection, which in turn can cause progressive corneal scarring, vascularisation, thinning and the need for corneal transplantation to recover vision, often with poor long‐term outcome. This study aimed to investigate peripheral cytokine production in HSK patients with active and inactive infection to identify potential therapeutic targets. Methods Peripheral blood mononuclear cells and serum were prepared from whole blood taken from both healthy controls and HSK patients during active infection or following treatment. Protein expression levels were analysed by Western Blot. Cytokine levels were determined by multiplex ELISA . Results Active corneal HSV ‐1 infection resulted in significantly elevated peripheral levels of the pro‐inflammatory cytokine IL ‐1b in patients compared to healthy controls. IL ‐1 β levels remained significantly increased in these patients following treatment. Impaired production of pro‐inflammatory cytokines (including IL ‐6, IL ‐8 and TNF ‐a) and anti‐viral factors (including IL ‐12 and IFN ‐g) was associated with significantly reduced expression of the transcription factors IRF 3 and STAT 1 in active patients compared to inactive patients. Conclusions Our data suggest that dysregulated peripheral production of pro‐inflammatory cytokines and anti‐viral factors may have implications for HSV ‐1 viral clearance and recurrent keratitis.