Endotoxin-induced uveitis (EIU) in the rat: a study of inflammatory and immunological mechanisms.
Endotoxin-induced uveitis (EIU) can be produced by systemic injection of endotoxin (ET). It is not clear yet why exclusive ocular involvement occurs in this model. To clarify this question and to establish the sequence of inflammatory events, EIU was induced in Lewis rats by footpad injection of Salmonella ET. Ocular inflammatory response (anterior chamber cells and proteins), aqueous inflammation mediators (thromboxane B2, prostaglandin E2, leukotriene B4 and substance P) and MHC class 2 (Ia) antigen expression in the ciliary body were monitored for 72 hours. Thromboxane B2 was detected early in the aqueous humor, peaking already 1 hour after ET injection. Prostaglandin E2 & leukotriene B4 peaks and a second peak of thromboxane B2 were recorded 18 hours after ET-injection, at the time of maximal ocular inflammation. MHC-class 2 expression was first detected in the ciliary body stroma at the vascular level 6 hours after ET injection and was massively expressed in the ciliary body epithelium at 18 and 72 hours. It is hypothesized that ciliary body endothelium is particularly sensitive to the effect of ET and is the site of thrombocyte adherence. Vascular damage leads in succession to cellular infiltration, release of inflammation mediators and disruption of blood-ocular barrier. MHC-class 2 expression is a secondary phenomenon and is probably at the origin of additional tissue damage from immune effector mechanisms.
Okumura
A
A
Department of Ophthalmology, School of Medicine, University of Tokyo, Japan.
Mochizuki
M
M
Nishi
M
M
Herbort
C P
CP
D000818:Animals; D001082:Aqueous Humor / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins; D002452:Cell Count; D002924:Ciliary Body / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004731:Endotoxins; D004768:Enterotoxins; D005136:Eye Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007249:Inflammation; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013373:Substance P / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism
D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II; C027952:salmonella toxin; D007975:Leukotriene B4; D013373:Substance P; D013929:Thromboxane B2; D015232:Dinoprostone