Procollagens and inflammatory cytokine concentrations in tarsal and limbal vernal keratoconjunctivitis.
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-beta 1, IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha, 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-beta 1 and TNF were identified in several active VKC patients without significant differences between the tarsal and the limbal forms. IL-1 beta (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-beta 1 and IL-6 were both significantly increased compared to controls (P < 0.01) while no increases were observed in IL-1 and TNF-alpha. (3) In serum, IL-1 alpha, IL-1 beta and TNF-alpha were higher in VKC patients compared to controls. (4) In vitro fibroblasts from VKC patients showed an increased production of TGF-beta 1, IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, PICP, and PIIIP over time. Increased levels of TGF-beta 1, 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-beta 1, IL-1 and IL-6. Increased serum levels of IL-1 and TNF-alpha suggests 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.
Institute of Physiopathological Optics, University of Padova, Italy.
A
A
Leonardi
F
F
Borghesan
M
M
DePaoli
M
M
Plebani
A G
AG
Secchi
D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D002648:Child; D003228:Conjunctiva / Q000737:chemistry*; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000378:metabolism*; D046508:Culture Techniques; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D011347:Procollagen / Q000032:analysis* / Q000097:blood; D013666:Tears / Q000737:chemistry* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis
D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D011347:Procollagen; D016212:Transforming Growth Factor beta; C042813:procollagen type I carboxy terminal peptide