[Effects of IL-1 receptor antagonist on the level of cytokine in the rat corneal grafts and aqueous humor after corneal transplantation].
OBJECTIVE
By detecting the expression of IL-1RI and TGF-beta(1) on the normal rat cornea and graft, and the amount of IL-1 beta in the aqueous humor of normal rat eye and the eye after keratoplasty, to investigate the relationship between these cytokines and graft rejection and to observe the effects of IL-1 receptor antagonist (IL-1ra) on graft rejection.


METHODS
All rats after keratoplasty were divided into five groups. Immunohistochemistry method and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of IL-1RI and TGF-beta(1) on the normal rat cornea and graft and the amount of IL- 1 beta in the aqueous humor of normal rat eye and the eye after keratoplasty at different time points: pre-rejection, acute-rejection and two weeks after surgery.


RESULTS
IL-1RI could be detected in normal rat cornea. TGF-beta(1) expressed mainly in the epithelium of normal cornea, especially the basal cell layer and the basement membrane. After keratoplasty, IL-1RI and TGF-beta(1) could be detected in the corneal epithelium, stroma and endothelium, and the level of expression decreased in sequence as negative control group, 50 micro g IL-1ra group, 100 micro g IL-1ra group, 200 micro g IL-1ra group and dexamethasone group. In the acute rejection period, the expression of IL-1RI and TGF-beta(1) in the 200 micro g IL-1ra group was less than that of the 50 micro g IL-1ra group, the difference was significant (P < 0.01). The expression of IL-1RI and TGF-beta(1) in the negative control group was higher than that of all experimental groups, the difference was significant (P < 0.01). IL-1 beta was detected in normal aqueous humor; the mean level was (96.0 +/- 11.3) ng/L. In the eye after keratoplasty, the IL-1 beta level increased significantly compared to normal aqueous humor (P < 0.01). In the acute rejection period, the quantity of IL-1 beta reached its peak at (552.2 +/- 68.3) ng/L in the negative control group, which was the highest quantity of IL-1 beta in all experimental groups (P < 0.01). The IL-1 beta level in all experimental groups in the pre-rejection period had no difference compared with that in the acute rejection period (P > 0.05), but the level of IL-1 beta in the pre-rejection and rejection periods was significantly different compared with that in the post-rejection period (P < 0.01).


CONCLUSIONS
IL-1RI and TGF-beta(1) play a active role in the corneal graft immunogenic rejection. IL-1 beta is a key factor in starting corneal graft rejection. The keratoplasty graft rejecting reaction can be reduced and mean survival time can be prolonged by IL-1ra, which inhibits the expression of IL-1RI and TGF-beta(1) and decreases the level of IL-1 beta in the aqueous humor.
Zhang
Wen-hua
WH
Beijing Institute of Ophthalmology, Beijing Tongren Ophthalmic Center, Capital University of Medical Science, Beijing 100730, China. panxiaow@public3.bta.net.cn
Zhai
Chang-bin
CB
Pan
Zhi-qiang
ZQ
Wu
Yu-ying
YY
D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry*; D003315:Cornea / Q000737:chemistry*; D016039:Corneal Transplantation; D016207:Cytokines / Q000032:analysis*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D017472:Receptors, Interleukin-1 / Q000032:analysis; D012795:Sialoglycoproteins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis
D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D003907:Dexamethasone