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Inhibition of endotoxin-induced uveitis and potentiation of local TNF-alpha and interleukin-6 mRNA expression by interleukin-13.
Invest Ophthalmol Vis Sci 1999; 40(10):2275-82IO

Abstract

PURPOSE

To investigate the effect of systemic injections of interleukin (IL)-13 on the development of endotoxin-induced uveitis (EIU) in the rat.

METHODS

EIU was induced in Lewis rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. Rats were treated with a subcutaneous injection in the back of recombinant human IL-13 (50 microg/kg in 0.2 ml of saline) performed 30 minutes before LPS injection and 6 and 10 hours afterward. At 23 hours after LPS injection, EIU was evaluated by slit-lamp examination and by counts of inflammatory cells on cryostat sections after specific immunostaining. The expression of nitric oxide synthase (NOS)-II in ocular tissues was determined by dual immunofluorescent staining and the release of nitrite in aqueous humor by Griess reaction. Cytokine gene expression in the iris/ciliary body, choroid, and retina was evaluated by reverse transcription-polymerase chain reaction.

RESULTS

At 24 hours after LPS injection, significant clinical inhibition of ocular inflammation and fibrin deposition in the eye was observed in IL-13-treated rats. Quantitative analysis of ocular tissues revealed a significant decrease of OX42+ cells (microglia, activated macrophages, dendritic cells, and polymorphonuclear leukocytes) and ED-1+ cells (monocytes/macrophages and dendritic cells). No effect on ED2+ cells (resident tissue macrophages) was found. Treatment with IL-13 decreased nitrite levels in aqueous humor and enhanced the expression of tumor necrosis factor-alpha (TNF-alpha) and IL-6 mRNA in ocular tissues.

CONCLUSIONS

Interleukin-13 treatment inhibits LPS-induced ocular inflammation with inhibition of nitrite release and increased TNF and IL-6 production in the eye. These results confirm the role of the NO pathway in the pathogenesis of EIU and suggest the involvement of TNF and IL-6 in the downregulation of ocular inflammation.

Authors+Show Affiliations

INSERM U450, Development, Aging and Pathology of the Retina, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10476793

Citation

Marie, O, et al. "Inhibition of Endotoxin-induced Uveitis and Potentiation of Local TNF-alpha and Interleukin-6 mRNA Expression By Interleukin-13." Investigative Ophthalmology & Visual Science, vol. 40, no. 10, 1999, pp. 2275-82.
Marie O, Thillaye-Goldenberg B, Naud MC, et al. Inhibition of endotoxin-induced uveitis and potentiation of local TNF-alpha and interleukin-6 mRNA expression by interleukin-13. Invest Ophthalmol Vis Sci. 1999;40(10):2275-82.
Marie, O., Thillaye-Goldenberg, B., Naud, M. C., & de Kozak, Y. (1999). Inhibition of endotoxin-induced uveitis and potentiation of local TNF-alpha and interleukin-6 mRNA expression by interleukin-13. Investigative Ophthalmology & Visual Science, 40(10), pp. 2275-82.
Marie O, et al. Inhibition of Endotoxin-induced Uveitis and Potentiation of Local TNF-alpha and Interleukin-6 mRNA Expression By Interleukin-13. Invest Ophthalmol Vis Sci. 1999;40(10):2275-82. PubMed PMID: 10476793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of endotoxin-induced uveitis and potentiation of local TNF-alpha and interleukin-6 mRNA expression by interleukin-13. AU - Marie,O, AU - Thillaye-Goldenberg,B, AU - Naud,M C, AU - de Kozak,Y, PY - 1999/9/7/pubmed PY - 1999/9/7/medline PY - 1999/9/7/entrez SP - 2275 EP - 82 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 40 IS - 10 N2 - PURPOSE: To investigate the effect of systemic injections of interleukin (IL)-13 on the development of endotoxin-induced uveitis (EIU) in the rat. METHODS: EIU was induced in Lewis rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. Rats were treated with a subcutaneous injection in the back of recombinant human IL-13 (50 microg/kg in 0.2 ml of saline) performed 30 minutes before LPS injection and 6 and 10 hours afterward. At 23 hours after LPS injection, EIU was evaluated by slit-lamp examination and by counts of inflammatory cells on cryostat sections after specific immunostaining. The expression of nitric oxide synthase (NOS)-II in ocular tissues was determined by dual immunofluorescent staining and the release of nitrite in aqueous humor by Griess reaction. Cytokine gene expression in the iris/ciliary body, choroid, and retina was evaluated by reverse transcription-polymerase chain reaction. RESULTS: At 24 hours after LPS injection, significant clinical inhibition of ocular inflammation and fibrin deposition in the eye was observed in IL-13-treated rats. Quantitative analysis of ocular tissues revealed a significant decrease of OX42+ cells (microglia, activated macrophages, dendritic cells, and polymorphonuclear leukocytes) and ED-1+ cells (monocytes/macrophages and dendritic cells). No effect on ED2+ cells (resident tissue macrophages) was found. Treatment with IL-13 decreased nitrite levels in aqueous humor and enhanced the expression of tumor necrosis factor-alpha (TNF-alpha) and IL-6 mRNA in ocular tissues. CONCLUSIONS: Interleukin-13 treatment inhibits LPS-induced ocular inflammation with inhibition of nitrite release and increased TNF and IL-6 production in the eye. These results confirm the role of the NO pathway in the pathogenesis of EIU and suggest the involvement of TNF and IL-6 in the downregulation of ocular inflammation. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/10476793/Inhibition_of_endotoxin_induced_uveitis_and_potentiation_of_local_TNF_alpha_and_interleukin_6_mRNA_expression_by_interleukin_13_ L2 - http://iovs.arvojournals.org/article.aspx?volume=40&page=2275 DB - PRIME DP - Unbound Medicine ER -