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Activity of an Interleukin 1 Receptor Antagonist in Rabbit Models of Uveitis

Activity of an Interleukin 1 Receptor Antagonist in Rabbit Models of Uveitis Abstract • Interleukin 1 has been implicated in intraocular inflammation. The availability of a cloned, recombinant interleukin 1 receptor antagonist has enabled us to test the role of interleukin 1 in specific models of uveitis in New Zealand white rabbits. Seventy-five micrograms of interleukin 1 receptor antagonist injected intravitreally resulted in a 97% reduction in aqueous humor cells present 6 hours after intravitreal injection of 10 ng of human interleukin 1 α. Disruption of the blood aqueous barrier was prevented by the receptor antagonist (mean SD aqueous humor protein of 0.6±0.1 g/L in rabbits treated with interleukin 1 receptor antagonist vs 32.2±9.9 g/L in controls). Lower doses of interleukin 1 produced more modest but significant inhibition. Despite the activity of interleukin 1 receptor antagonist in inhibiting interleukin 1-induced inflammation, interleukin 1 receptor antagonist did not produce significant reduction in inflammation subsequent to an active Arthus reaction or subsequent to the intravitreal injection of 125 ng of endotoxin. A potential explanation of these observations is that cytokines in addition to interleukin 1 may be present in sufficient quantities to produce intraocular inflammation or that the effects of interleukin 1 may be primarily intracellular (intracrine) and therefore resistant to the activity of exogenously administered receptor antagonist. References 1. Nouri AME, Panayi GS, Goodman SM. Cytokines and the chronic inflammation of rheumatic disease, I: the presence of interleukin-1 in synovial fluids . Clin Exp Immunol . 1984;55:295-302. 2. Dinarello CA, Cannon JG, Mier JW, et al. Multiple biological activities of human recombinant interleukin-1 . J Clin Invest . 1986;77:1734-1739.Crossref 3. Cybulsky MI, Colditz IG, Movat HZ. The role of interleukin-1 in neutrophil leukocyte emigration induced by endotoxin . Am J Pathol . 1986;124:367-372. 4. Leizer T, Hamilton JA. Plasminogen activator and prostaglandin E2 levels in human synovial fibroblasts . J Immunol . 1989;143:971-978. 5. Seckinger P, Klein-nulend J, Alander C, Thompson RC, Dayer J-M, Raisz LG. Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production . J Immunol . 1990;145:4181-4184. 6. Luscinskas FW, Cybulsky MI, Kiely J-M, Peckins CS, Davis VM, Gimbrone MA Jr. Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 . J Immunol . 1991;146:1617-1625. 7. Abe Y, Sekiya S, Yamasita T, Sendo F. Vascular hyperpermeability induced by tumor necrosis factor and its augmentation by IL-1 and IFN-gamma is inhibited by selective depletion of neutrophils with a monoclonal antibody . J Immunol . 1990;145:2902-2907. 8. Davis JL, Jalkh AE, Roberge F, et al. Subretinal fluid from human retinal detachment contains interleukin-1 . Invest Ophthalmol Vis Sci . 1988;29:396. 9. Rosenbaum JT, Samples JR, Hefeneider SH, Howes EL Jr. Ocular inflammatory effects of intravitreal interleukin-1 . Arch Ophthalmol . 1987;105:1117-1120.Crossref 10. Planck SR, Dang TT, Ansel JC, Robertson JE, Rosenbaum JT. Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1 . Invest Ophthalmol Vis Sci . 1990;31:372-372. 11. Ansel JC, Tara D, Rosenbaum JT. Synthesis of interleukins 1 and 6 by human cornea . Invest Ophthalmol Vis Sci . 1991;32:676. Abstract. 12. Roberge FG, Caspi RR, Nussenblatt RB. Glial retinal Muller cells produce Il-1 activity and have a dual effect on autoimmune T helper lymphocytes . J Immunol . 1988;140:2193-2196. 13. Hannum CH, Wilcox CJ, Arend WP, et al. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor . Nature . 1990;343:336-340.Crossref 14. Arend WP, Joslin FG, Thompson RC, Hannum CH. An IL-1 inhibitor from human monocytes: production and characterization of biologic properties . J Immunol . 1989;143:1851-1858. 15. Bienkowski MJ, Eessalu TE, Berger AE, et al. Purification and characterization of interleukin 1 receptor level antagonist proteins from THP-1 cells . J Biol Chem . 1990;265:14505-14511. 16. Ohlsson K, Bjork P, Bergenfeldt M, et al. Human IL-1 inhibitor (IL-li) blocks the effects of IL-1 beta in the rabbit . Cytokine . 1989;1:131. 17. Wooley PH, Whalen JD, Chapman DL, Berger AE, Aspar DG, Richard KA. The effect of an interleukin-1 receptor antagonist protein on type II collagen and antigen-induced arthritis in mice . Arthritis Rheum . 1990;33:S20. 18. Rosenbaum JT, Raymond W. Monocyte chemotactic activity induced by intravitreal endotoxin . Invest Ophthalmol Vis Sci . 1985;26:1267-1273. 19. Rosenbaum JT, Seymour BWP, Raymond W, Langlois L. Wu M, David L. A similar chemotactic factor for monocytes predominates in different animal models of uveitis . Inflammation . 1988;12:191-201.Crossref 20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding . Anal Biochem . 1976;72:248-254.Crossref 21. Dinarello CA. Biology of interleukin 1 . FASEB J . 1988;2:108-115. 22. Cominelli F, Nast CC, Clark BD, et al. Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis . J Clin Invest . 1990;86:972-980.Crossref 23. Czachowski CL, Coffey JW, Meyers KP. Treatment with recombinant IL-1 receptor antagonist (IL-lra) suppresses the development of zymosan-induced pleurisy . FASEB J . 1991;5:A634. Abstract. 24. Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock . Nature . 1990;348:550-552.Crossref 25. Wakabayashi G, Gelfand JA, Burke JF, Thompson R, Dinarello CA. A specific receptor antagonist for interleukin 1 prevents Escherichia coli induced shock in rabbits . FASEB J . 1991;5:308-313. 26. Ulich TR, Yin S, Guo K, Del Castillo J, Eisenberg SP, Thompson RC. The intratracheal administration of endotoxin and cytokines, III: the interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation . Am J Pathol . 1991;138:521-524. 27. Kupper TS, Lee F, Birchall N, et al. Interleukin 1 binds to specific receptors on human keratinocytes and induces granulocyte macrophage colony-stimulating factor mRNA and protein . J Clin Invest . 1988;82:1787-1792.Crossref 28. Fincham NJ, Camp RDR, Gearing AJH, Bird CR, Cunningnam FM. Neutrophil chemoattractant and IL-1-like activity in samples from psoriatic skin lesions: further characterization . J Immunol . 1988;140:4294-4299. 29. Bigler CF, Weston WL, Norris DA, Arend WP. Interleukin-1 receptor antagonist production by human keratinocytes . Clin Res . 1991;39:291a. Abstract. 30. Helle M, Boeije L, Aarden LA. 11-6 is an intermediate in Il-1-induced thymocyte proliferation . J Immunol . 1989;142:4335-4338. 31. Katz Y, Strunk RC. Il-1 and tumor necrosis factor: similarities and differences in stimulation of expression of alternative pathway of complement and IFN-B2/Il-6 genes in human fibroblasts . J Immunol . 1989;142:3862-3867. 32. Elner VM, Strieter RM, Elner SG, Baggiolini M, Lindley I, Kunkel S. Neutrophilchemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells . Am J Pathol . 1990;136:745-750. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Activity of an Interleukin 1 Receptor Antagonist in Rabbit Models of Uveitis

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Publisher
American Medical Association
Copyright
Copyright © 1992 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1992.01080160125049
Publisher site
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Abstract

Abstract • Interleukin 1 has been implicated in intraocular inflammation. The availability of a cloned, recombinant interleukin 1 receptor antagonist has enabled us to test the role of interleukin 1 in specific models of uveitis in New Zealand white rabbits. Seventy-five micrograms of interleukin 1 receptor antagonist injected intravitreally resulted in a 97% reduction in aqueous humor cells present 6 hours after intravitreal injection of 10 ng of human interleukin 1 α. Disruption of the blood aqueous barrier was prevented by the receptor antagonist (mean SD aqueous humor protein of 0.6±0.1 g/L in rabbits treated with interleukin 1 receptor antagonist vs 32.2±9.9 g/L in controls). Lower doses of interleukin 1 produced more modest but significant inhibition. Despite the activity of interleukin 1 receptor antagonist in inhibiting interleukin 1-induced inflammation, interleukin 1 receptor antagonist did not produce significant reduction in inflammation subsequent to an active Arthus reaction or subsequent to the intravitreal injection of 125 ng of endotoxin. A potential explanation of these observations is that cytokines in addition to interleukin 1 may be present in sufficient quantities to produce intraocular inflammation or that the effects of interleukin 1 may be primarily intracellular (intracrine) and therefore resistant to the activity of exogenously administered receptor antagonist. References 1. Nouri AME, Panayi GS, Goodman SM. Cytokines and the chronic inflammation of rheumatic disease, I: the presence of interleukin-1 in synovial fluids . Clin Exp Immunol . 1984;55:295-302. 2. Dinarello CA, Cannon JG, Mier JW, et al. Multiple biological activities of human recombinant interleukin-1 . J Clin Invest . 1986;77:1734-1739.Crossref 3. Cybulsky MI, Colditz IG, Movat HZ. The role of interleukin-1 in neutrophil leukocyte emigration induced by endotoxin . Am J Pathol . 1986;124:367-372. 4. Leizer T, Hamilton JA. Plasminogen activator and prostaglandin E2 levels in human synovial fibroblasts . J Immunol . 1989;143:971-978. 5. Seckinger P, Klein-nulend J, Alander C, Thompson RC, Dayer J-M, Raisz LG. Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production . J Immunol . 1990;145:4181-4184. 6. Luscinskas FW, Cybulsky MI, Kiely J-M, Peckins CS, Davis VM, Gimbrone MA Jr. Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 . J Immunol . 1991;146:1617-1625. 7. Abe Y, Sekiya S, Yamasita T, Sendo F. Vascular hyperpermeability induced by tumor necrosis factor and its augmentation by IL-1 and IFN-gamma is inhibited by selective depletion of neutrophils with a monoclonal antibody . J Immunol . 1990;145:2902-2907. 8. Davis JL, Jalkh AE, Roberge F, et al. Subretinal fluid from human retinal detachment contains interleukin-1 . Invest Ophthalmol Vis Sci . 1988;29:396. 9. Rosenbaum JT, Samples JR, Hefeneider SH, Howes EL Jr. Ocular inflammatory effects of intravitreal interleukin-1 . Arch Ophthalmol . 1987;105:1117-1120.Crossref 10. Planck SR, Dang TT, Ansel JC, Robertson JE, Rosenbaum JT. Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1 . Invest Ophthalmol Vis Sci . 1990;31:372-372. 11. Ansel JC, Tara D, Rosenbaum JT. Synthesis of interleukins 1 and 6 by human cornea . Invest Ophthalmol Vis Sci . 1991;32:676. Abstract. 12. Roberge FG, Caspi RR, Nussenblatt RB. Glial retinal Muller cells produce Il-1 activity and have a dual effect on autoimmune T helper lymphocytes . J Immunol . 1988;140:2193-2196. 13. Hannum CH, Wilcox CJ, Arend WP, et al. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor . Nature . 1990;343:336-340.Crossref 14. Arend WP, Joslin FG, Thompson RC, Hannum CH. An IL-1 inhibitor from human monocytes: production and characterization of biologic properties . J Immunol . 1989;143:1851-1858. 15. Bienkowski MJ, Eessalu TE, Berger AE, et al. Purification and characterization of interleukin 1 receptor level antagonist proteins from THP-1 cells . J Biol Chem . 1990;265:14505-14511. 16. Ohlsson K, Bjork P, Bergenfeldt M, et al. Human IL-1 inhibitor (IL-li) blocks the effects of IL-1 beta in the rabbit . Cytokine . 1989;1:131. 17. Wooley PH, Whalen JD, Chapman DL, Berger AE, Aspar DG, Richard KA. The effect of an interleukin-1 receptor antagonist protein on type II collagen and antigen-induced arthritis in mice . Arthritis Rheum . 1990;33:S20. 18. Rosenbaum JT, Raymond W. Monocyte chemotactic activity induced by intravitreal endotoxin . Invest Ophthalmol Vis Sci . 1985;26:1267-1273. 19. Rosenbaum JT, Seymour BWP, Raymond W, Langlois L. Wu M, David L. A similar chemotactic factor for monocytes predominates in different animal models of uveitis . Inflammation . 1988;12:191-201.Crossref 20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding . Anal Biochem . 1976;72:248-254.Crossref 21. Dinarello CA. Biology of interleukin 1 . FASEB J . 1988;2:108-115. 22. Cominelli F, Nast CC, Clark BD, et al. Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis . J Clin Invest . 1990;86:972-980.Crossref 23. Czachowski CL, Coffey JW, Meyers KP. Treatment with recombinant IL-1 receptor antagonist (IL-lra) suppresses the development of zymosan-induced pleurisy . FASEB J . 1991;5:A634. Abstract. 24. Ohlsson K, Bjork P, Bergenfeldt M, Hageman R, Thompson RC. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock . Nature . 1990;348:550-552.Crossref 25. Wakabayashi G, Gelfand JA, Burke JF, Thompson R, Dinarello CA. A specific receptor antagonist for interleukin 1 prevents Escherichia coli induced shock in rabbits . FASEB J . 1991;5:308-313. 26. Ulich TR, Yin S, Guo K, Del Castillo J, Eisenberg SP, Thompson RC. The intratracheal administration of endotoxin and cytokines, III: the interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation . Am J Pathol . 1991;138:521-524. 27. Kupper TS, Lee F, Birchall N, et al. Interleukin 1 binds to specific receptors on human keratinocytes and induces granulocyte macrophage colony-stimulating factor mRNA and protein . J Clin Invest . 1988;82:1787-1792.Crossref 28. Fincham NJ, Camp RDR, Gearing AJH, Bird CR, Cunningnam FM. Neutrophil chemoattractant and IL-1-like activity in samples from psoriatic skin lesions: further characterization . J Immunol . 1988;140:4294-4299. 29. Bigler CF, Weston WL, Norris DA, Arend WP. Interleukin-1 receptor antagonist production by human keratinocytes . Clin Res . 1991;39:291a. Abstract. 30. Helle M, Boeije L, Aarden LA. 11-6 is an intermediate in Il-1-induced thymocyte proliferation . J Immunol . 1989;142:4335-4338. 31. Katz Y, Strunk RC. Il-1 and tumor necrosis factor: similarities and differences in stimulation of expression of alternative pathway of complement and IFN-B2/Il-6 genes in human fibroblasts . J Immunol . 1989;142:3862-3867. 32. Elner VM, Strieter RM, Elner SG, Baggiolini M, Lindley I, Kunkel S. Neutrophilchemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells . Am J Pathol . 1990;136:745-750.

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Apr 1, 1992

References

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