Selective control of formation of 1 and 2 series prostaglandins: a new concept in the regulation of inflammation and immunity

  • D. F. Horrobin
  • M. S. Manku
  • M. Oka
  • S. C. Cunnane
Part of the Inflammation: Mechanisms and Treatment book series (FTIN, volume 4)


The roles of prostaglandins (PGs) and thromboxanes (TXs) in inflammation are uncertain. There can be no doubt that these agents are formed in increased amounts in a wide variety of inflammatory conditions and that inhibition of that formation by steroids and by non-steroidal anti-inflammatory drugs (NSAID) is well correlated with relief of symptoms in both acute and chronic inflammatory conditions in humans and with suppression of some of the features of acute inflammation in animal models. On the other hand, there is equally no doubt that glucocorticoids and NSAID do not favourably influence the long-term course of most chronic inflammatory states in humans1. Furthermore there is a good deal of evidence that PGs can play antiinflammatory roles2–5.


Familial Mediterranean Fever Essential Fatty Acid Selective Control Intracellular Calcium Release Cystic Fibrosis46 
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  1. 1.
    Lewis, G. P. (1978). Inflammation, with emphasis on its mediation. Ann.R. Coll. Surg. Eng: 60, 192Google Scholar
  2. 2.
    Bonta, I. L. and Parnham, M. J. (1978). Time-dependent pro- and anti-inflammatory effects of prostagland in E1on experimental granulomata in rats. Br. J. Pharmacol., 62, 417PGoogle Scholar
  3. 3.
    Kulonen, E. and Potila, M. (1975). Effect of the administration of antirheumatic drugs on experimental granuloma in the rat. Biochem. Pharmacol., 24, 417PGoogle Scholar
  4. 4.
    James, G. W. L. and Church, M. K. (1978). Hyperalgesia after treatment of mice with prostaglandins and arachidonic acid and its antagonism by anti-inflammatory compounds. Arzneim. Forsch., 28, 804Google Scholar
  5. 5.
    Bonta, I. L., Bult, H., Parnham, M.J. and Vincent, J. E. (1978). Inflammatory models in rats depleted of endogenous precursors of prostaglandins. Agents Actions, 8, 98PubMedCrossRefGoogle Scholar
  6. 6.
    Goldyne, M. E. (1977). Prostaglandins and the modulation of immunological responses. Int. J. Dermatol, 16, 701PubMedCrossRefGoogle Scholar
  7. 7.
    Ishizuka, M., Taeuchi, T. and Umezawa, H. (1974). Promotion of antibody formation by prostaglandin. Experientia, 30, 1207PubMedCrossRefGoogle Scholar
  8. 8.
    Plescia, O. J., Smith, A. H. and Grinwick, K. (1975). Subversion ofimmune system by tumor cells and role of prostaglandins. Proc. Natl. Acad. Sci. (USA), 72, 1848CrossRefGoogle Scholar
  9. 9.
    Krakauer, K., Torrey, S. B. and Zurier, R. B. (1978). Prostaglandin E1treatment of NZB/W mice. III. Clin. Immunol. Immunopathol., 11, 256PubMedCrossRefGoogle Scholar
  10. 10.
    Webb, E. R. and Osheroff, P. L. (1976). Antigen stimulation of prostaglandin synthesis and control of immune responses. Proc. Natl. Acad. Sci. (USA), 73, 1300CrossRefGoogle Scholar
  11. 11.
    Quagliata, F., Lawrence, V. J. W. and Phillips-Quagliata, J. M. (1973). Prostaglandin E, as a regulator of lymphocyte function. Cell. Immunol., 6, 457PubMedCrossRefGoogle Scholar
  12. 12.
    Famaey, J.P., Fontaine, J. and Reuse, J. (1976). The effects of D-penicillamine on ileal smooth muscle and their possible relationships with prostaglandins. In Munthe, E. (ed.) Penicillamine: Research in Rheumatoid Disease, pp. 50–57. (Rahway: Merck Sharp & Dohme).Google Scholar
  13. 13.
    Cunnane, S. C., Zinner, H., Horrobin, D. F. et al.(1979). Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2and I2and penicillamine. Can. J. Physiol. Pharmacol., 57, 35PubMedCrossRefGoogle Scholar
  14. 14.
    Robinson, D. R., Smith, H., McGuire, M.B. and Levine, L. (1975). Prostaglandin synthesis by rheumatoid synovia and its stimulation by colchicine. Prostaglandins, 10, 67PubMedGoogle Scholar
  15. 15.
    Floman, Y. (1978). Prostaglandin E production by cultured inflamed rat synovium: stimulation by colchicine and inhibition by chloroquine. Prostaglandins Med., 1, 39PubMedCrossRefGoogle Scholar
  16. 16.
    Goldfinger, S. E. (1972). Colchicine for familial Mediterranean fever. New Eng. J. Med., 287, 1302PubMedGoogle Scholar
  17. 17.
    Lehman, T. J. A., Peters, R. S., Hanson, V. and Schwabe, A. D. (1978). Long term colchicine therapy of familial Mediterranean fever. J. Pediatr., 93, 876PubMedCrossRefGoogle Scholar
  18. 18.
    Hazen, P. G., and Michel, B. (1979: Management of necrotizing vasculitis with colchicine. Arch. Dermatol., 115, 1303PubMedCrossRefGoogle Scholar
  19. 19.
    Kloeze, J. (1969). Relationship between chemical structure and platelet aggregation activity of prostaglandins. Biochim. Biophys. Acta, 187, 285PubMedGoogle Scholar
  20. 20.
    Kunkel, S. L., Thrall, R. S., Kunkel, R. G. et al.(1976). Suppression of immune complex vasculitis in rats by prostaglandin. J. Clin. Invest., 64, 1525CrossRefGoogle Scholar
  21. 21.
    Feinstein, M. B., Becker, E. L. and Fraser, C. (1977). Thrombin, collagen and A23187 stimulated platelet arachidonate metabolism: differential inhibition by PGE1, local anesthetics and a serine-protease inhibitor. Prostaglandins, 14, 1075PubMedCrossRefGoogle Scholar
  22. 22.
    Minkes, M., Stanford, N., Chi, M. M. Y. et al.(1977). Cyclic adenosine monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions. J. Clin. Invest., 59, 449PubMedCrossRefGoogle Scholar
  23. 23.
    Manku, M. S., Horrobin, D. F., Karmazyn, M. and Cunnane, S. C. (1979) Prolactin and zinc effects on rat vascular reactivity: possible relationship to dihomogammalinolenic acid and to prostagland in synthesis. Endocrinology, 104, 774PubMedCrossRefGoogle Scholar
  24. 24.
    Kirtland, S. J. and Baum, H. (1972). Prostaglandin E1may act as a calcium ionophore. Nature (London) New Biol., 236, 47CrossRefGoogle Scholar
  25. 25.
    Manku, M. S. and Horrobin, D. F. (1976). Indomethacin inhibits responses to all vasoconstrictors in the rat mesenteric vascular bed: restoration of responses by prostaglandin E2. Prostaglandins, 12, 369PubMedCrossRefGoogle Scholar
  26. 26.
    Manku, M. S., Oka, M. and Horrobin, D. F. (1979). Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. 1. Effects of ethanol. Prostaglandins Med., 3, 119PubMedCrossRefGoogle Scholar
  27. 27.
    Manku, M.S., Oka, M. and Horrobin, D. F. (1979). Differential regulation of the formation of prostaglandins and related substances from arachidonic acid and from dihomogammalinolenic acid. 11. Effects of vitamin C. Prostaglandins Med., 3, 129PubMedCrossRefGoogle Scholar
  28. 28.
    Horrobin, D. F. (1979). Cellular basis of prolactin action: involvement of cyclic nucleotides, polyamines, prostaglandins, steroids, thyroid hormones, Na/K ATPases and calcium: relevance to breast cancer and the menstrual cycle. Med. Hypotheses, 5, 599PubMedCrossRefGoogle Scholar
  29. 29.
    Horrobin, D. F. (1978). Prostaglandins: Physiology, Pharmacology and Clinical Significance.(Edinburgh: Churchill Livingstone)Google Scholar
  30. 30.
    Cunnane, S. C., Horrobin, D. F., Manku, M. S. et al.(1980). The vascular response to zinc varies seasonally: effects of pinealectomy and melatonin. Chronobiologia, (In press)Google Scholar
  31. 31.
    Kondo, K., Manku, M. A., Horrobin, D. F. et al.(1977). Potentiation of the pressor effects of noradrenaline and potassium ions in rat mesenteric arteries by physiological levels of angiotensin II: effects of prostaglandin E2 and Cortisol. Clin. Sci. Mol. Med., 53, 233PubMedGoogle Scholar
  32. 32.
    Karmazyn, M., Manku, M. S. and Horrobin, D. F. (1978). Changes of vascular reactivity induced by low vasopressin concentrations: interactions with Cortisol and lithium and possible involvement of prostaglandins. Endocrinology, 102, 1230PubMedCrossRefGoogle Scholar
  33. 33.
    Karmazyn, M., Horrobin, D. F., Manku, M. S. et al.(1977). Myo-Inositol in physiological concentrations stimulates production of prostaglandin-like material. Prostaglandins, 14, 967PubMedCrossRefGoogle Scholar
  34. 34.
    Manku, M. S., Horrobin, D. F., Scidah, N. and Chretien, M. (1977). Beta-endorphin inhibits the effects of prolactin on synthesis of PGE1-like material. Presented at the International Conference on Central Nervous System Effects of Hypothalamic Hormones and Other Peptides, Montreal, May 2.Google Scholar
  35. 35.
    Bell, R. L, Kennedy, D. A., Stanford, N. and Majerus, P. W. (1979). Diglyceride lipase: a pathway for arachidonate release from human platelets. Proc. Natl. Acad. Sci. (USA), 76, 3238CrossRefGoogle Scholar
  36. 36.
    Rittenhouse-Simmons, S. (1979). Production of diglycerides from phosphatidyl inositol in activated human platelets. J. Clin. Invest., 63, 580PubMedCrossRefGoogle Scholar
  37. 37.
    Boot, J. R., Dawson, W. and Kitchen, E. A. (1976). The chemotactic activity of thromboxane B2: a possible role in inflammation. J. Physiol., 257, 47PGoogle Scholar
  38. 38.
    Malawista, S. E. (1975). The action of colchicine in acute gouty arthritis. Arthritis Rheum., 18, 835PubMedCrossRefGoogle Scholar
  39. 39.
    Horrobin, D. F., Manku, M.S., Karmali, R. A. et al.(1978). Thromboxane A2: a key regulator of prostaglandin biosynthesis and of interactions between prostaglandins, calcium and cyclic nucleotides. Med. Hypotheses, 4, 178PubMedCrossRefGoogle Scholar
  40. 40.
    Horrobin, D. F., Oka, M. and Manku, M. S. (1978). Thromboxane A2as a regulator of prostaglandin synthesis. Relevance to interactions between colchicine and histidine in the control of inflammation. Eur. J. Rheum., 2, 181Google Scholar
  41. 41.
    Fitzgerald, T.J. and Veal, A. (1976). Melatonin antagonizes colchicine-induced mitotic arrest. Experientia, 32, 372PubMedCrossRefGoogle Scholar
  42. 42.
    Malawista, S.E. (1971). The melanocyte model. Colchicine-like effects of other anit-mitotic agents. J. Cell Biol, 49, 848PubMedCrossRefGoogle Scholar
  43. 43.
    Birau, N. and Schloot, W. (1979). Pathological nyctohemeral rhythm of melatonin secretion in psoriasis, Klinefelter’s syndrome and spina bifida. IRCS J. Med. Sci., 7, 400Google Scholar
  44. 44.
    Hammarstrom, S., Hamberg, M., Duell, E. A. et al.(1975). Increased concentrations of non-esterified arachidonic acid, 12L-hydroxy-5,8,10,14-eicosatrienoic acid, prostaglandin E2and prostaglandin F2alpha in epidermis of psoriasis. Proc. Natl. Acad. Sci. (USA), 72, 5130CrossRefGoogle Scholar
  45. 45.
    Malkinson, F. E. and Lynfield, Y. L. (1959). Colchicine alopecia. J. Invest. Dermatol., 33, 371PubMedCrossRefGoogle Scholar
  46. 46.
    Horrobin, D. F., Manku, M. S., Oka, M. et al.(1979). The nutritional regulation of Tlymphocyte function. Med. Hypotheses, 5, 969PubMedCrossRefGoogle Scholar
  47. 47.
    Chase, H. P. and Dupont, J. (1978). Abnormal levels of prostaglandins and fatty acids in blood of children with cystic fibrosis. Lancet, 2, 36Google Scholar
  48. 48.
    McCormick, J. N., Neill, W. A. and Sim, A. K. (1977). Immunosuppressive effect of linoleic acid. Lancet, 2, 508PubMedCrossRefGoogle Scholar
  49. 49.
    Dunbar, L. M. and Bailey, J. M. (1975). Enzyme deletions and essential fatty acid metabolism in cultured cells. J. Biol. Chem., 250, 1152Google Scholar
  50. 50.
    Horrobin, D. F., Oka, M. and Manku, M. S. (1979). The regulation of prostaglandin E1formation: a candidate for one of the fundamental mechanisms involved in the actions of vitamin C. Med. Hypotheses, 5, 849PubMedCrossRefGoogle Scholar
  51. 51.
    Horrobin, D. F. and Cunnane, S. C. (1980). Interactions between zinc, essential fatty acids and prostaglandins: relevance to acrodermatitis enteropathica, total parenteral nutrition, the glucagonoma syndrome, diabetes, anorexia nervosa and sickle cell anaemia. Med. Hypotheses, 6, 277PubMedCrossRefGoogle Scholar
  52. 52.
    Johnson, M., Jessup, R. and Ramwell, P. (1973). Ultraviolet light modification of the prostaglandin receptor. Prostaglandins, 4. 593CrossRefGoogle Scholar
  53. 53.
    Manku, M.S., Horrobin, D. F., Oka, M. et al.(1978). Ultra-violet radiation and 8-methoxypsoralen have actions similar to those of known inhibitors of thromboxane A2synthesis in rat mesenteric blood vessels. Prostaglandins Med., 1, 86PubMedCrossRefGoogle Scholar
  54. 54.
    Farrant, J. and Knight, S. C. (1979). Help and suppression by lymphoid cells as a function of cellular concentration. Proc. Natl. Acad. Sci. (USA), 76, 3507CrossRefGoogle Scholar
  55. 55.
    Eardley, D.D., Staskawicz, M.O. and Gershon, R. K. (1976). Suppressor cells: dependence on assay conditions for functional activity. J. Exp. Med., 143, 1211PubMedCrossRefGoogle Scholar
  56. 56.
    Dekel, S., Falconer, J. and Francis, M. J. O. (1980): The effect of anti-inflammatory drugs on glycosaminoglycan sulphation in pig cartilage. Prostaglandins Med., 4, 133PubMedCrossRefGoogle Scholar
  57. 57.
    Horrobin, D. F. and Campbell, A. (1980). Sjogren’s syndrome and the sicca syndrome: the role of prostaglandin E. deficiency. Treatment with essential fatty acids and vitamin C. Med. Hypotheses, 6, 225PubMedCrossRefGoogle Scholar
  58. 58.
    Horrobin, D. F. (1979). Schizophrenia: reconciliation of the dopamine, prostaglandin and opioid concepts and the role of the pineal. Lancet, 1, 529PubMedCrossRefGoogle Scholar
  59. 59.
    Mery, C., Delrieu, F., Ghozlan, R. et al. (1976). A controlled trial of D-penicillamine in rheumatoid arthritis — dose effect and the role of zinc. Scand. J. Rheumatol., 5, 241PubMedCrossRefGoogle Scholar
  60. 60.
    Manku, M. S. and Horrobin, D. F. (1976). Chloroquine, quinine, procaine, quinidine, tricyclic antidepressants and methyl xanthines are prostglandin agonists and antagonists. Lancet, 2,1115PubMedCrossRefGoogle Scholar
  61. 61.
    Alarcon-Segovia, D., Ibanez, G. and Kershenobich, D. (1974). Treatment of scleroderma by modification of collagen metabolism. A double blind trial with colchicine versus placebo. J. Rheumatol, 1, 97Google Scholar
  62. 62.
    Trnavska, Z., Mikulikova, D. and Trnavsky, K. (1977). The effects of colchicine and its derivatives on collagen biosynthesis in vitro. Agents Actions, 7, 563CrossRefGoogle Scholar
  63. 63.
    Gerber, D. A. (1975). Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity. J. Clon. Invest., 55, 1164CrossRefGoogle Scholar
  64. 64.
    Karmali, R. A., Hanrahan, R., Volkman, A. and Smith, N. (1980). Regulation of autoimmunity and development of antibodies to DNA in NZB/W mice (Submitted for publication)Google Scholar

Copyright information

© MTP Press Limited 1980

Authors and Affiliations

  • D. F. Horrobin
    • 1
  • M. S. Manku
    • 1
  • M. Oka
    • 1
  • S. C. Cunnane
    • 1
  1. 1.Canada

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