Procollagens and Inflammatory Cytokine Concentrations in Tarsal and Limbal Vernal Keratoconjunctivitis

• Published in: Experimental eye research Vol. 67; no. 1; pp. 105 - 112
• Main Authors: LEONARDI, A., BORGHESAN, F., DePAOLI, M., PLEBANI, M., SECCHI, A.G.
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 01.07.1998; Elsevier
• Subjects: Adolescent; Biological and medical sciences; Biomarkers - analysis; Cells, Cultured; Child; Conjunctiva - chemistry; Conjunctivitis, Allergic - immunology; Conjunctivitis, Allergic - metabolism; Culture Techniques; Cytokines - analysis; Cytokines - blood; Diseases of eyelid, conjunctiva and lacrimal tracts; Female; Fibroblasts - chemistry; Humans; IL-1; IL-6; Interleukin-1 - analysis; Interleukin-6 - analysis; Male; Medical sciences; Ophthalmology; Peptide Fragments - analysis; Procollagen - analysis; Procollagen - blood; procollagens I and III; Tears - chemistry; Tears - immunology; TGF-β1; TNF-α; Transforming Growth Factor beta - analysis; vernal keratoconjunctivitis; vernal keratoconjunctivitis; TGF-β1; procollagens I and III; TNF-α; IL-1; IL-6; Human; Allergy; Immunopathology; Procollagen; Cytokine; Vernal conjunctivitis; Inflammation; Conjunctiva disease; Interleukin 6; Eye disease; Keratoconjunctivitis; Interleukin 1; Transforming growth factor β1; Tumor necrosis factor α
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1006/exer.1998.0499

To quantify the presence of inflammatory/fibrogenic cytokines and procollagens type I (PICP) and III (PIIIP) in active and non-active tarsal and limbal forms of vernal keratoconjunctivitis (VKC), tear and blood samples were collected from 27 VKC patients (20 active and 7 non-active) and 15 normal subjects. Upper tarsal conjunctival biopses were obtained from 8 controls and 8 tarsal VKC patients. From biopses of 4 tarsal VKC, fibroblasts were cultured in F12 medium with 10% FCS. TGF-β1, IL-1α, IL-1β, IL-6 and TNF-α, PICP and PIIIP were measured in: (1) tears, (2) homogenized conjunctival tissues, (3) serum, (4) supernatants of tissue cultures at 24 hr, and fibroblast primary passage cultures. Results showed: (1) in tears, TGF-β1 and TNF were identified in several active VKC patients without significant differences between the tarsal and the limbal forms. IL-1β(27±51 pg ml−1,P=0.03) and IL-6 (28±43 pg ml−1,P=0.006) were significantly increased in tarsal VKC compared to controls. Both control and non-active VKC tear samples had undetectable levels of all of the above cytokines. PICP and PIIIP were significantly increased in tarsal VKC compared to both limbal VKC and controls. Non-active VKC levels were similar to controls. (2) In homogenized VKC tissues, TGF-β1 and IL-6 were both significantly increased compared to controls (P<0.01) while no increases were observed in IL-1 and TNF-α. (3) In serum, IL-1α, IL-1β and TNF-αwere higher in VKC patients compared to controls. (4) In vitro fibroblasts from VKC patients showed an increased production of TGF-β1, IL-1α, IL-1β, IL-6, TNF-α, PICP, and PIIIP over time. Increased levels of TGF-β1, IL-1 and IL-6 in VKC tissues and tears indicate a local production of these cytokines in active VKC. Collagen hyperproduction occurs only in active tarsal VKC and may be related to high levels of TGF-β1, IL-1 and IL-6. Increased serum levels of IL-1 and TNF-αsuggests that systemic immunological changes occur in VKC. Cell culture can be used as a model to further study the pathogenesis of VKC and its characteristic local fibroblast activation.