Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.

Abstract

Interleukin I (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-la and (3 mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-la was significantly elevated at 4 h (9.4±1.5 ng/g colon), progressively increased at 48 h (31±5.8 ng/g) and then decreased by 96 h (11.5±3.4 ng/g). IL-lft levels were 2.0±0.5 ng/g colon at 4 h, 5.0±1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-la levels were highly correlated with inflammation (r = 0.885, P < 0.0001), edema (r = 0.789, P < 0.0001) and necrosis (r = 0.752, P < 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-Ira) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2±0.4 to 1.4±0.3, P < 0.02), edema (from 2.2±0.4 to 0.6±0.3, P < 0.01) and necrosis (from 43±10% to 6.6±3.2%, P < 0.03) compared to vehicle-matched colitis animals. These studies demonstrate

Mice Transgenic for IL-1 Receptor Antagonist Protein Are Resistant to Herpetic Stromal Keratitis: Possible Role for IL-1 in Herpetic Stromal Keratitis Pathogenesis

“…The aim of this study was to determine whether inhibition of IL-1, as could be achieved by using a transgenic mouse that overexpressed the IL-1 receptor antagonist (IL-1ra), had an effect on SK pathogenesis. Such transgenic mice have been used in other inflammatory models and were shown to block IL-1 and diminish disease expression (15)(16)(17)(18). Our results with ocular infection with HSV demonstrate that IL-1ra transgenic (IL-1ra Tg) mice developed significantly milder disease and reduced corneal angiogenesis compared with IL-1ra Ϫ/Ϫ and C57BL/6 mice.…”

Omega-3 Fatty Acid-Derived Mediators 17(R)-Hydroxy Docosahexaenoic Acid, Aspirin-Triggered Resolvin D1 and Resolvin D2 Prevent Experimental Colitis in Mice

“…The cytokines TNF-a and IL-1b play a pivotal role in pathogenesis of human and experimental colitis (42,43), and Abs against TNF-a are largely used in the clinical treatment of IBD (44). Previous reports have demonstrated that RvE1 treatment abolishes colonic mRNA expression of TNF-a and IL-1b in DSSand TNBS-induced colitis (7,25), which are associated with a dramatic inhibition of PMN infiltration of the intestinal mucosa.…”

Allelic polymorphism in IL-1β and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease

“…The proteins encoded by the IL-1 a and IL-1/3 genes appear to play an important role in chronic IBD, since enhanced production of IL-1 has been reported in gut tissue of animal models of intestinal inflammation [13,14], as well as in the mucosa [15] and isolated cell preparations of patients with active IBD [16,17].…”