Intraocular Injection of Prostaglandins: Modification of Response to Circulating Bacterial Endotoxin

Keye L. Wong; Edward Lee Howes

doi:10.1001/archopht.1983.01040010277019

Wong, Keye L.;Howes, Edward Lee

1983-02-01 00:00:00

Abstract • Circulating bacterial endotoxin in the rabbit produces a transient iridocyclitis. Alteration in the ocular vascular permeability was measured by accumulation of iodonated I 125 serum albumin. The role of local mediator release in modifying the effect of endotoxin was investigated by pretreatment with intravitreal injections of prostaglandin E2 (alprostadil), prostaglandin E2 (dinoprostone), prostaglandin F2α (dinoprost), histamine dihydrochloride, histamine phosphate, bradykinin triacetate, and serotonin creatinine sulfate. Histamine, bradykinin, and serotonin by themselves did not produce an alteration in ocular vascular permeability in the manner studied, nor did their prior injection alter the ocular response to circulating endotoxin. By contrast, prostaglandin E1, prostaglandin E2, and prostaglandin F2α produced an alteration in ocular vascular permeability. After resolution of this alteration, the eye became partially refractory to endotoxin-induced inflammation. Neither the production of an inhibitory substance nor cyclic adenosine monophosphate seemed to be involved in this decreased responsiveness. Possible mechanisms of this anti-inflammatory effect are discussed. References 1. Howes EL Jr, Aronson SB, McKay DG: Ocular vascular permeability: Effect of systemic administration of bacterial endotoxin . Arch Ophthalmol 1970;84:360-367.Crossref 2. Ayo C: Toxic ocular reaction: New property of Schwartzman toxins . J Immunol 1943;46:113-125. 3. Morrison DC, Ulevich RJ: The effects of bacterial endotoxins on host mediation systems: A review . Am J Pathol 1978;93:526-617. 4. Whitelocke RAF, Eakins KE, Bennet A: Acute anterior uveitis and prostaglandins . Proc R Soc Med 1973;66:429. 5. Eakins KE, Whitelocke RAF, Perkins ES, et al: Release of prostaglandins in ocular inflammation in rabbits . Nature New Biol 1972;239:248-249.Crossref 6. Eakins KE: Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier . Exp Eye Res 1977;25( (suppl) ):483-498.Crossref 7. Howes EL Jr, McKay DG: The effects of aspirin and indomethacin on the ocular response to circulating bacterial endotoxin in the rabbit . Invest Ophthalmol Vis Sci 1976;15:648-651. 8. Howes EL Jr, McKay DG: Comparison of the ocular effects of circulating endotoxin and immune complexes: Role of vasoactive amines . J Immunol 1975;114:734-737. 9. Hogan MJ, Kimura SJ, Thygeson P: Signs and symptoms of uveitis: Anterior uveitis . Am J Ophthalmol 1959;47:155-170. 10. Lowry OH, Rosebrough JJ, Farr AL, et al: Protein measurement with the Folin phenol reagent . J Biol Chem 1951;193:265-275. 11. Beavo JA, Rogers NL, Crofford OB, et al: Effects of xanthine derivatives on lipolysis and on adenosine 3',5'-monophosphate phosphodiesterase activity . Mol Pharmacol 1970;6:597-603. 12. Howes EL Jr, McKay DG, Aronson SB: An ultrastructural study of the ciliary process in the rabbit following systemic administration of bacterial endotoxin . Lab Invest 1971;24:217-228. 13. Kaley G, Weiner R: Prostaglandin E,: A potential mediator of the inflammatory response . Ann NY Acad Sci 1971;180:338-350.Crossref 14. Cole DF: The site of breakdown of the blood-aqueous barrier under the influence of vaso-dilator drugs . Exp Eye Res 1974;19:591-607.Crossref 15. Eakins KE, Bhattacherjee P: Histamine prostaglandins and ocular inflammation . Exp Eye Res 1977;24:299-305.Crossref 16. Ashton N, Cunha-Vaz JG: Effect of histamine on the permeability of the ocular vessels . Arch Ophthalmol 1965;73:211-223.Crossref 17. Thomas G, West GB: Prostaglandins, kinin and inflammation in the rat . Br J Pharmacol 1974;50:231-235.Crossref 18. Saeed SA, McDonald-Gibson WJ, Cuthbert J, et al: Endogenous inhibitors of prostaglandin synthetase . Nature 1977;270:32-36.Crossref 19. Ferreira SH: Prostaglandins , in Houck JG (ed): Chemical Messengers of the Inflammatory Process . New York, Elsevier/North-Holland Inc, 1979. 20. Bourne HR, Lichtenstein LM, Melmon KL, et al: Modulation of inflammation and immunity by cyclic AMP . Science 1974;184:19-28.Crossref 21. Neufeld AH, Sears ML: Cyclic-AMP in ocular tissues of the rabbit, monkey, and human . Invest Ophthalmol Vis Sci 1974;13:475-477. 22. Weissman G, Smolen JE, Korchak H: Prostaglandins and inflammation: Receptor/cyclase coupling as an explanation of why PgE's and PGI2 inhibit functions of inflammatory cells . Adv Prostaglandin Thromboxane Res 1980;8:1637-1653. 23. Zurier RB, Quagliata F: Effect of prostaglandin El on adjuvant arthritis . Nature 1971;234:304-305.Crossref 24. Kunkel SL, Thrall RS, Kunkel RG, et al: Suppression of immune complex vasculitis in rats by prostaglandin . J Clin Invest 1979;64:1525-1529.Crossref 25. Melmon KL, Rocklin RE, Rosenkranz RP: Autocoids as modulators of the inflammatory and immune response . Am J Med 1981;71:100-106.Crossref 26. Kunkel SL, Ogawa H, Connan PB, et al: Suppression of acute and chronic inflammation by orally administered prostaglandins . Arthritis Rheum 1981;24:1151-1158.Crossref

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Archives of Ophthalmology American Medical Association

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Intraocular Injection of Prostaglandins: Modification of Response to Circulating Bacterial Endotoxin

$Abstract • Circulating bacterial endotoxin in the rabbit produces a transient iridocyclitis. Alteration in the ocular vascular permeability was measured by accumulation of iodonated I 125 serum albumin. The role of local mediator release in modifying the effect of endotoxin was investigated by pretreatment with intravitreal injections of prostaglandin E2 (alprostadil), prostaglandin E2 (dinoprostone), prostaglandin F2α (dinoprost), histamine dihydrochloride, histamine phosphate, bradykinin triacetate, and serotonin creatinine sulfate. Histamine, bradykinin, and serotonin by themselves did not produce an alteration in ocular vascular permeability in the manner studied, nor did their prior injection alter the ocular response to circulating endotoxin. By contrast, prostaglandin E1, prostaglandin E2, and prostaglandin F2α produced an alteration in ocular vascular permeability. After resolution of this alteration, the eye became partially refractory to endotoxin-induced inflammation. Neither the production of an inhibitory substance nor cyclic adenosine monophosphate seemed to be involved in this decreased responsiveness. Possible mechanisms of this anti-inflammatory effect are discussed. References 1. Howes EL Jr, Aronson SB, McKay DG: Ocular vascular permeability: Effect of systemic administration of bacterial endotoxin . Arch Ophthalmol 1970;84:360-367.Crossref 2. Ayo C: Toxic ocular reaction: New property of Schwartzman toxins . J Immunol 1943;46:113-125. 3. Morrison DC, Ulevich RJ: The effects of bacterial endotoxins on host mediation systems: A review . Am J Pathol 1978;93:526-617. 4. Whitelocke RAF, Eakins KE, Bennet A: Acute anterior uveitis and prostaglandins . Proc R Soc Med 1973;66:429. 5. Eakins KE, Whitelocke RAF, Perkins ES, et al: Release of prostaglandins in ocular inflammation in rabbits . Nature New Biol 1972;239:248-249.Crossref 6. Eakins KE: Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier . Exp Eye Res 1977;25( (suppl) ):483-498.Crossref 7. Howes EL Jr, McKay DG: The effects of aspirin and indomethacin on the ocular response to circulating bacterial endotoxin in the rabbit . Invest Ophthalmol Vis Sci 1976;15:648-651. 8. Howes EL Jr, McKay DG: Comparison of the ocular effects of circulating endotoxin and immune complexes: Role of vasoactive amines . J Immunol 1975;114:734-737. 9. Hogan MJ, Kimura SJ, Thygeson P: Signs and symptoms of uveitis: Anterior uveitis . Am J Ophthalmol 1959;47:155-170. 10. Lowry OH, Rosebrough JJ, Farr AL, et al: Protein measurement with the Folin phenol reagent . J Biol Chem 1951;193:265-275. 11. Beavo JA, Rogers NL, Crofford OB, et al: Effects of xanthine derivatives on lipolysis and on adenosine 3',5'-monophosphate phosphodiesterase activity . Mol Pharmacol 1970;6:597-603. 12. Howes EL Jr, McKay DG, Aronson SB: An ultrastructural study of the ciliary process in the rabbit following systemic administration of bacterial endotoxin . Lab Invest 1971;24:217-228. 13. Kaley G, Weiner R: Prostaglandin E,: A potential mediator of the inflammatory response . Ann NY Acad Sci 1971;180:338-350.Crossref 14. Cole DF: The site of breakdown of the blood-aqueous barrier under the influence of vaso-dilator drugs . Exp Eye Res 1974;19:591-607.Crossref 15. Eakins KE, Bhattacherjee P: Histamine prostaglandins and ocular inflammation . Exp Eye Res 1977;24:299-305.Crossref 16. Ashton N, Cunha-Vaz JG: Effect of histamine on the permeability of the ocular vessels . Arch Ophthalmol 1965;73:211-223.Crossref 17. Thomas G, West GB: Prostaglandins, kinin and inflammation in the rat . Br J Pharmacol 1974;50:231-235.Crossref 18. Saeed SA, McDonald-Gibson WJ, Cuthbert J, et al: Endogenous inhibitors of prostaglandin synthetase . Nature 1977;270:32-36.Crossref 19. Ferreira SH: Prostaglandins , in Houck JG (ed): Chemical Messengers of the Inflammatory Process . New York, Elsevier/North-Holland Inc, 1979. 20. Bourne HR, Lichtenstein LM, Melmon KL, et al: Modulation of inflammation and immunity by cyclic AMP . Science 1974;184:19-28.Crossref 21. Neufeld AH, Sears ML: Cyclic-AMP in ocular tissues of the rabbit, monkey, and human . Invest Ophthalmol Vis Sci 1974;13:475-477. 22. Weissman G, Smolen JE, Korchak H: Prostaglandins and inflammation: Receptor/cyclase coupling as an explanation of why PgE's and PGI2 inhibit functions of inflammatory cells . Adv Prostaglandin Thromboxane Res 1980;8:1637-1653. 23. Zurier RB, Quagliata F: Effect of prostaglandin El on adjuvant arthritis . Nature 1971;234:304-305.Crossref 24. Kunkel SL, Thrall RS, Kunkel RG, et al: Suppression of immune complex vasculitis in rats by prostaglandin . J Clin Invest 1979;64:1525-1529.Crossref 25. Melmon KL, Rocklin RE, Rosenkranz RP: Autocoids as modulators of the inflammatory and immune response . Am J Med 1981;71:100-106.Crossref 26. Kunkel SL, Ogawa H, Connan PB, et al: Suppression of acute and chronic inflammation by orally administered prostaglandins . Arthritis Rheum 1981;24:1151-1158.Crossref$

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Intraocular Injection of Prostaglandins: Modification of Response to Circulating Bacterial Endotoxin

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