Oxygen is an important factor in pathogenesis of retinopathy of prematurity(ROP). Proinflammatory cytokines are among the factors mediating the hyperoxic damage. Interleukin-1 (IL-1) is a major cytokine participating in inflammatory response. Another cytokine, IL-1 receptor antagonist (IL-1ra) binds to the IL-1 receptors but does not elicit the intracellular signal transduction. Being a specific antagonist to IL-1, IL-1ra is an anti-inflammatory cytokine. The aim of the present study was to investigate whether hyperoxia and/or glucocorticoid affect the growth of the retinal vessels, and the expression of the anti-inflammatory cytokine IL-1ra. Altogether four groups of newborn rabbits were studied during days 3 and 12: group 1. animals were in room air and received placebo (n=6); group 2. animals received dexamethasone (DX, at 1 mg/mg/day during days 3 to 8) (n=6); group 3. animals were kept in 100% O2 during days 3 to 7 and received placebo (n=10); group 4. animals were kept in O2 and received DX (n=10). Day 12 the eyes were studied for retinal vessel length, and for expression of IL-1ra mRNA in the retina using the Northern blot analysis. According to the present results: 1. hyperoxia decreased the length of the retinal vessels by 75%, and increased the incidence of neovascularization (4 of 6 eyes); 2. the glucocorticoid decreased the axial length of the retinal vessels by 64%, increased the tortuosity of the retinal vessels, and did not cause neovascularization; 3. O2 and DX tended potentiate each others actions in vessel growth inhibition; 4. O2 decreased the expression of IL-1ra m-RNA by 70%; 5. DX had no effect on IL-1ra expression, and did not potentiate the suppression of IL-1ra by hyperoxia. According to present results the inhibition of retinal vessel growth by the glucocorticoid was not associated with neovascularization or with altered expression of IL-1ra. The hyperoxia-induced suppression of the retinal anti-inflammatory cytokine, IL-1ra, serves as an evidence that proinflammatory cytokines are involved in the pathogenesis of ROP.
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Lawas, P., Hernandez, H., Bry, K. et al. EXPRESSION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST IN RETINA: EFFECTS OF HYPEROXIA AND GLUCOCORTICOID. † 1331. Pediatr Res 39 (Suppl 4), 224 (1996). https://doi.org/10.1203/00006450-199604001-01354
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DOI: https://doi.org/10.1203/00006450-199604001-01354