The suppressive role of interleukin-10 on the experimental endotoxin-induced uveitis

Abstract

Objective To examine the role of recombinant interleukin-10 (IL-10) and the therapeutic effect of endotoxin-induced uveitis (EIU) in rats. Methods Fifty-six male Wistar rats were randomized into three groups. IL-10 treatment group and positive control group had 24 rats respectively, and the normal control group had eight rats. Endotoxin-induced uveitis (EIU) is an established animal model of acute ocular inflammation induced by LPS intravenous injection ( 1 μg/kg). The onset times and signs were observed and the clinical scores were recorded. The blood samples and the aqueous humor samples of right eye were collected separately before the rats were sacrificed at fourth hour, 24th hour and third day after LPS injection. The enzyme-linked immunosorbent assay was used to measure tumor necrosis factor (TNF) α,IL-6, and IL-10 levels in the serum and aqueous humor. The left eyes were used for pathological examination and pathological grading. Results The symptoms of uveitis were appeared in all 24 rats in the positive group. The average onset time was (3.81 ± 1.05) hours, the average clinical score was 3.67±l. 97. The mild manifestations of uveitis were also appeared in all of the rats in treatment group. The average onset time was (5. 63±1.02) hours, the average clinical score was 2.00± 1.25. The average onset time in treatment group was postponed compared with the rats of positive group (t=4.95, P=0. 000).The clinical scores (t= 3. 50, P= 0. 00) and the pathological grades (t= 3.28, P= 0. 00) in treatment group were lower than those of positive group. There were not signs or pathologic changes in all the eight rats in the negative control group. The serum and aqueous humor levels of TNF-α and IL-6 in the rats of positive group were higher than those of the treatment group and control group (F=15.34, 57.65, 67.59, 8.42;P=0. 00). The serum and aqueous humor levels of IL-10 in the rats of treatment group were higher than those of the positive group and the control group (F = 17.84, 7.76; P = 0.00). There were positive correlations between the level of aqueous humor TNF-α, serum and aqueous humor levels of IL-6 and the disease severity (reye=0. 58, 0. 31, 0. 81, rpath =0. 56, 0. 31, 0. 74; P＜0.05). The negative correlations were presented between the serum levels of IL-10 with the disease severity (r=- 0. 54,-0. 55; P= 0.00).There were negative correlations between the serum and aqueous humor levels of TNF-α and IL-6 and the onset timeof the disease (r=-0.47,-0.59,-0.77,-0.36; P＜0.05) as well. Conclusions These findings strongly suggest that suppressive IL-10 is a potent candidate for the prevention of TNF-α and IL-6 in uveitis and could be applied as a novel immunoregulatory agent to control EIU. Key words: Uveitis/drug therapy; Interleukin-10/therapeutic use; Endotoxins; Animal experimentation