engleski

Profile of Cytokines in Aqueous Humor from Corneal Graft Recipients

Aim. Due to the immune privilege of the anterior eye chamber, the success rate of corneal transplantation can reach 90%. The aim of this study was to determine cytokine profile in aqueous humor of patients undergoing corneal transplantation, and to establish whether cytokine profile at the time of surgery influenced corneal graft outcome. Methods. Proinflammatory (TNF-b&#61472 ; and IFN-g) and immunosuppressive (TGF-b2) cytokine levels were measured in aqueous humor and serum of 44 patients. Non-inflammatory corneal diseases included keratoconus (n=8), bullous keratopathy (n=7), and stromal dystrophy (n=3). Inflammatory diseases included corneal scars (n=10), graft rejection (n=5), pending perforation (n=4), chemical burns (n=4), rejection/ uveitis (n=1), infectious keratitis (n=1), and perforated ulcer (n=1). Control aqueous humor and sera were obtained from cadavers without corneal pathology. Results. The concentration of TGF-b2 in the aqueous humor in non-inflammatory corneal diseases was similar to that of controls (2, 605 &plusmn ; 204 pg/mL vs 2, 200 &plusmn ; 100 pg/mL). In inflammatory corneal diseases, the concentration of TGF-b2 in aqueous humor was significantly lower (1, 400 &plusmn ; 375 pg/mL, p<0.001). TNF-b &#61472 ; was detected in the aqueous humor of 16 out of 26 patients with inflammatory corneal diseases and in all patients with stromal dystrophies, but was undetectable in cases of keratoconus and bullous keratopathy. Low levels of IFN-g &#61472 ; were present in all aqueous humor samples. Patients&#8217 ; sera contained significantly less cytokine (up to 252 pg/mL) then their aqueous humor (p<0.001). We have set an arbitrary cut-off point for TGF-b2 level in aqueous humor at 1, 500 pg/mL and divided all investigated samples (from 44 patients and 10 controls) into two groups, one with high and the other with low TGF-b2 concentration. The coefficient of contingency showed that patients with high TGF-b2 concentration in their aqueous humor had significantly greater chance for graft acceptance than those with low TGF-b2 concentration (p<0.001). Conclusion. High TGF- b2 concentrations in the eyes without intraocular inflammation suggest its immunosuppressive role in human eyes. High concentration of TGF-b2 (>1, 500 pg/mL) was associated with graft acceptance. Also, absence of proinflamatory TNF-b&#61472 ; increased the graft acceptance, but independently from TGF- b2. Key words: aqueous humor ; corneal disease ; corneal transplantation ; cytokines ; eye diseases ; graft survival ; immune toler-ance ; immunosuppression ; inflammation ; interferon type II ; transforming growth factor ; tumor necrosis factor Cytokines are short-lived molecules that act pri-marily in the local milieu in picomolar to nanomolar concentrations to regulate host cell function. Since they are effective at very low concentrations, small changes in their concentration may result in profound changes in the immunoinflammatory response. The intraocular microenvironment is an immune-privileged site where immunogenic inflammation has been associated with immunosuppressive factors found in aqueous humor produced by ocular tissues. For example, transforming growth factor-beta (TGF-b) can suppress immune cell activity, as shown in the anterior chamber of the eye (1). The abrogation of the intraocular immune privilege is associated with the presence of proinflammatory cyto-kines, e.g., in uveitis or allograft rejection (2-9). It seems that the character of immune response at specific site may be determined by the set of released cytokines (10). Immune privilege of the anterior eye chamber was recorded over 100 years ago, when researchers found that xenogeneic tumor grafts survived signifi-cantly longer in the anterior chamber than at other sites (11-13). The first hypothesis trying to explain the phenomenon was that the antigens placed in the ante-rior chamber were sequestered, and therefore the af- ferent blockade of the immune system was present (11). However, it has became clear that antigens placed in the eye had the access to the systemic circu-lation (13, 14), and that the graft survived due to the immunoregulatory processes within the anterior chamber, which resulted in the suppression of the de-layed type hypersensitivity to the antigen introduced through the anterior chamber (12, 13). The phenome-non where the inoculation of the antigen via the ante-rior chamber depresses the cell-mediated immune re-sponse to that specific antigen is called anterior cham-ber- associated immune deviation (15). Cytokines are mediators of the immunosuppressive properties of the anterior eye chamber

Cytokine profile; aqueous humor; corneal transplantation

nije evidentirano