Pro-Inflammatory Mediators and Human Skin Disease

  • Fiona M. Cunningham
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 181)

Abstract

Human skin diseases are many and diverse in nature, ranging from conditions where the primary abnormality is a transient disorder of the vasculature, one example being urticaria, to conditions such as psoriasis, which are characterised by a chronic cellular infiltrate. It has been suggested that the pathological changes associated with these skin diseases may be brought about by chemical mediators present in the involved tissue. Before any aspect of disease pathology is ascribed to the actions of a particular compound, however, certain criteria must first be satisfied. The mediator, should be identified in lesional tissue and, ideally, the absolute amounts compared to those in clinically normal skin. If other compounds with similar modes of actions are also present it is useful to ascertain the relative amounts of each since, although one mediator may be considerably less potent in eliciting a particular response, the difference in potency may be rendered of little importance if that compound is present in correspondingly greater amounts in vivo. The ability of cells derived from the skin to produce the mediator in vitro following stimulation suggests that release from the resident skin cell population may contribute to the endogenous levels measured, although whether such release is a primary event in the evolution of a lesion, or occurs secondarily in response to tissue damage cannot readily be determined.

Keywords

High Performance Liquid Chromatography Nicotinate Histamine Prostaglandin Vasculitis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    A. Kobza Black, M.W. Greaves, C.N. Hensby, N.A. Plummer and R.A.J. Eady, A new method for recovery of exudate from normal and inflamed human skin, Clin. exp. Dermatol. 2:209 (1977).PubMedCrossRefGoogle Scholar
  2. 2.
    S.F. Talbot, P.C. Atkins, E.J. Goetzl and B. Zweiman, Accumulation of leukotriene C4 and histamine in human allergic skin reactions, J. clin. Invest. 76:650 (1985).PubMedCrossRefGoogle Scholar
  3. 3.
    S. Brain, R. Camp, P. Dowd, A. Kobza Black and M.W. Greaves, The release of leukotriene B4-like material in biologically active amounts from the lesional skin of patients with psoriasis, J. Invest. Dermatol. 83:70 (1984).PubMedCrossRefGoogle Scholar
  4. 4.
    S. Hammarstrom, M. Hamberg, B. Samuelsson, E.A. Duell, M. Stawiski and J.J. Voorhees, Increased concentrations of non-esterified arachidonic acid, 12L-hydroxyeicosatetraenoic acid, Prostaglandin E2 and Prostaglandin F2 α in the epidermis of psoriasis, Proc. Natl. Acad. Sci. 72:5130 (1975).PubMedCrossRefGoogle Scholar
  5. 5.
    R.D.R. Camp, A.I. Mallet, P.M. Woollard, S.D. Brain, A. Kobza Black and M.W. Greaves, The identification of hydroxy fatty acids in psoriatic skin, Prostaglandins 26:431 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    S.D. Brain, R.D.R. Camp, A. Kobza Black, P.M. Dowd, M.W. Greaves, A.W. Ford-Hutchinson and S. Charleson, Leukotrienes C4 and D4 in psoriatic skin lesions, Prostaglandins 29:611 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    P.M. Woollard, Stereochemical difference between 12-hydroxy 5,8,10,14-eicosatetraenoic acid in platelets and psoriatic lesions, Biochem. Biophys. Res. Commun. 136:169 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    N. Fincham, R. Camp and I. Leigh, Synthesis of arachidonate lipoxygenase products by epidermal cells, J. Invest. Dermatol. 84:447 (1985).Google Scholar
  9. 9.
    J. Grabbe, T. Rosenbach and B. Czarnetzki, Production of LTB4-like chemotactic arachidonate metabolites from human keratinocytes, J. Invest. Dermatol. 85:527.Google Scholar
  10. 10.
    B.A. Burrall, B.W. Wintroub and E.J. Goetzl, Selective expression of 15-lipoxygenase activity by cultured human keratinocytes, Biochem. Biophys. Res. Commun. 133:208 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    B. Mayer, L. Rauter, E. Zenzmaier, H. Gleispach and H. Esterbauer, Characterisation of lipoxygenase metabolites of arachidonic acid in cultured human skin fibroblasts, Biochim. Biophys. Acta 795:151 (1984).PubMedGoogle Scholar
  12. 12.
    R. Camp, R. Russell Jones, S. Brain, P. Woollard and M. Greaves, Production of intraepidermal microabscesses by topical application of leukotriene B4, J. Invest. Dermatol. 82:202 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    F.M. Cunningham, P.M. Woollard and R.D.R. Camp, Proinflammatory properties of unsaturated fatty acids and their monohydroxy metabolites, Prostaglandins 30:497 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    P.M. Dowd, A. Kobza Black, R.D.R. Camp and M.W. Greaves, Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), J. Invest. Dermatol. 84:537 (1985).PubMedCrossRefGoogle Scholar
  15. 15.
    P.M. Woollard, G.M. Murphy, F.M. Cunningham, R.D.R. Camp and M.W. Greaves, Proinflammatory effects of 12(R)-hydroxy-5,8,10,14 eicosatetraenoic acid in human skin, Br. J. Dermatol. 118:277 (1988).Google Scholar
  16. 16.
    F.M. Cunningham and P.M. Woollard, 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid is a chemoattractant for human polymorphonuclear leukocytes in vitro, Prostaglandins 34:71 (1987).PubMedCrossRefGoogle Scholar
  17. 17.
    K.B. Bacon, R.D.R. Camp, F.M. Cunningham and P.M. Woollard, Contrasting in vitro lymphocyte chemotactic activity of the hydroxyl enantiomers of 12-hydroxy-5,8,10,14-eicosatetraenoic acid, Br. J. Pharmacol. 95:966 (1988).PubMedGoogle Scholar
  18. 18.
    E. Wong, R.D. Camp and M.W. Greaves, The responses of normal and psoriatic skin to single and multiple applications of leukotriene B4, J. Invest. Dermatol. 84:421 (1985).PubMedCrossRefGoogle Scholar
  19. 19.
    P.M. Dowd, A. Kobza Black, P.M. Woollard and M.W. Greaves, Cutaneous responses to 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and 5,12,-dihydroxyeicosatetraenoic acid (leukotriene B4) in psoriasis and normal human skin, Arch. Dermatol. Res. 279:427 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    L.S. Hong and L. Levine, Inhibition of arachidonic acid release from cells as the biochemical action of anti-inflammatory corticosteroids, Proc. Natl. Acad. Sci. 73:1730 (1976).PubMedCrossRefGoogle Scholar
  21. 21.
    R. Camp, A. Kobza Black, F. Cunningham, A. Mallet and M. Greaves, Pharmacological effects of topical lonapalene in psoriasis, J. Invest. Dermatol. 90:550 (1988).Google Scholar
  22. 22.
    R.M. Barr, A. Kobza Black, P.M. Dowd, O. Koro, K. Mistry, J.L. Isaacs and M.W. Greaves, The in vitro 5-lipoxygenase and cyclo-oxygenase inhibitor L-653–343 does not inhibit 5-lipoxygenase activity in vivo in human skin, Br. J. clin. Pharmacol. 25:23 (1988).PubMedGoogle Scholar
  23. 23.
    E. Wong, M.W. Greaves and T. O’Brien, Increased concentrations of immunoreactive leukotrienes in cutaneous lesions of eosinophilic cellulitis, Br. J. Dermatol. 110:653 (1984).PubMedCrossRefGoogle Scholar
  24. 24.
    W. Dorsch, J. Ring, P-C. Weber and T. Strasser, Detection of immunoreactive leukotrienes LTC4/D4 in skin-blister fluid after allergen testing in patients with late cutaneous reactions (LCR), Arch. Dermatol. Res. 277:400 (1985).PubMedCrossRefGoogle Scholar
  25. 25.
    R.M. Barr, S. Brain, R.D.R. Camp, J. Cilliers, M.W. Greaves, A.I. Mallet and K. Misch, Levels of arachidonic acid and its metabolites in the skin in human allergic and irritant contact dermatitis, Br. J. Dermatol. 111:23 (1984).PubMedCrossRefGoogle Scholar
  26. 26.
    T. Ruzicka, T. Simmet, B.A. Peskar and O. Braun-Falco, Leukotrienes in skin of atopic dermatitis, Lancet 1:222 (1984).PubMedCrossRefGoogle Scholar
  27. 27.
    T. Ruzicka, T. Simmet, B.A. Peskar and J. Ring, Skin levels of arachidonic acid-derived inflammatory mediators and histamine in atopic dermatitis and psoriasis, J. Invest. Dermatol. 86:105 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    R.D.R. Camp and F.M. Cunningham, The role of eicosanoids in inflammatory disorders of the skin, in: “Advances in Eicosanoid Research: Eicosanoids in inflammatory conditions of the lung, skin and joints” M. Church and C. Robinson ed., MTP Press, Lancaster/Boston/The Hague/Dordrecht (1988).Google Scholar
  29. 29.
    R.J. Flower, E.A. Harvey and W.P. Kingston, Inflammatory effects of Prostaglandin D2 in rat and human skin, Br. J. Pharmacol. 56:229 (1976).PubMedGoogle Scholar
  30. 30.
    M.M. Pienkowski, N.F. Adkinson, M. Plaut, P.S. Norman and L.M. Lichtenstein, Prostaglandin D2 and histamine during the immediate and the late-phase components of allergic cutaneous responses, J. Allergy clin. Immunol. 82:95 (1988).PubMedCrossRefGoogle Scholar
  31. 31.
    D.J. Heavey, A. Kobza Black, S.E. Barrow, C.G. Chappell, M.W. Greaves and C.T. Dollery, Prostaglandin D2 and histamine release in cold urticaria, J. Allergy clin. Immunol. 78:458 (1986)PubMedCrossRefGoogle Scholar
  32. 32.
    O. Koro, J.S. Dover, D.M. Francis, A. Kobza Black, R.W. Kelly, R.M. Barr, and M.W. Greaves, Release of Prostaglandin D2 and histamine in a case of localised heat urticaria, and effect of treatments, Br. J. Dermatol. 115:721 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    L.J. Roberts, B.J. Sweetman, R.A. Lewis, K.F. Austen and J.A. Oates, Increased production of Prostaglandin D2 in systemic mastocytosis, N. Eng. J. Med 303:1400 (1980).CrossRefGoogle Scholar
  34. 34.
    M. Greaves, Continuing Medical Education (therapy). Pharmacology and significance of non steroidal anti-inflammatory drugs in the treatment of skin diseases, Am. Acad. Dermatol. 16:751 (1987).CrossRefGoogle Scholar
  35. 35.
    W. Remy, I. Sigl and B. Leipold, Prostaglandin E2 gel improvement of psoriatic lesions, Int. J. Dermatol. 25:266 (1986).PubMedCrossRefGoogle Scholar
  36. 36.
    C.A. Demopoulos, R.N. Pinckard and D.J. Hanahan, Platelet activating factor. Evidence “for 1–0-alkyl-2-acetyl-sn-glyceryl-3-phosphoryl choline as the active component (a new class of lipid Chemical mediators), J. Biol. Chem. 254:9355 (1979).PubMedGoogle Scholar
  37. 37.
    C.B. Archer, C.P. Page, W. Paul, J. Morley and D.M. MacDonald, Inflammatory characteristics of platelet activating factor (PAF-acether) in human skin, Br. J. Dermatol. 110:45 (1984).PubMedCrossRefGoogle Scholar
  38. 38.
    C.B. Archer, C.P. Page, J. Morley and D.M. MacDonald, Accumulation of inflammatory cells in response to intracutaneous platelet activating factor (PAF-acether) in man, Br. J. Dermatol. 112:285 (1985).PubMedCrossRefGoogle Scholar
  39. 39.
    E. Henocq and B.B. Vargaftig, Skin eosinophilia in atopic patients, J. Allergy clin. Immunol. 79:248 (1987).Google Scholar
  40. 40.
    F. Valone, M. Shalit, P. Atkins, E. Goetzl and B. Sireiman, Platelet activating factor release in allergic skin sites in humans, J. Allergy clin. Immunol. 79:248 (1987).Google Scholar
  41. 41.
    L. Michel, Y. Denizot, Y. Thomas, J. Benveniste and L. Dubertret, Release of PAF-acether and precursors during allergic cutaneous reactions, Lancet II:404 (1988).CrossRefGoogle Scholar
  42. 42.
    N.M. Roberts, C.P. Page, K.F. Chung and P.J. Barnes, Effect of a PAF antagonist BN 52063 on antigen-induced acute and late-onset cutaneous responses in atopic subjects, J. Allergy clin. Immunol. 82:236 (1988).PubMedCrossRefGoogle Scholar
  43. 43.
    A.I. Mallet and F.M. Cunningham, Structural identification of platelet activating factor in psoriatic scale, Biochem. Biophy. Res. Commun. 126:192 (1985).CrossRefGoogle Scholar
  44. 44.
    C.S. Ramesha, N. Soter and W.C. Pickett, Identification and quantitation of PAF from psoriatic scales, Ag. Actions 21:382 (1987).CrossRefGoogle Scholar
  45. 45.
    A.I. Mallet, F.M. Cunningham, E. Wong and M.W. Greaves, Platelet activating factor in chronic plaque psoriasis in: “Adv. in Prostaglandin, Thromboxane and Leukotriene Res. Vol. 17” B. Samuelsson, R. Paoletti and P. Ramwell, eds. Raven Press, New York (1987).Google Scholar
  46. 46.
    L. Michel, Y Denizot, Y. Thomas, F. Jean-Louis, C. Pitton, J. Benveniste and L. Dubertret, Biosynthesis of PAF-acether factor acether by human skin fibroblasts in vitro, J. Immunol. 141:948 (1988).PubMedGoogle Scholar
  47. 47.
    F.M. Cunningham, I. Leigh and A.I. Mallet, The production of platelet activating factor (PAF) by human epidermal cells, Br. J. Pharmacol. 91:117P (1987).Google Scholar
  48. 48.
    K.E. Grandel, R.S. Farr, A.A. Wanderer, T.C. Eisenstadt and S.I. Wasserman, Association of platelet activating factor with primary acquired cold urticaria N. Eng. J. Med. 313:405 (1985).CrossRefGoogle Scholar
  49. 49.
    P. Braquet, L. Touqui, T.Y. Shen and B.B. Vargaftig, Perspectives in platelet activating factor research, Pharmacol. Revs. 39:97 (1987).Google Scholar
  50. 50.
    B. Fjellner and O. Hagermark, Experimental pruritus evoked by platelet activating factor (PAF-acether) in man, Acta Derm. Venereol. 65:409 (1985).PubMedGoogle Scholar
  51. 51.
    Ph. Guinot, C. Summerhays, L. Berdah, J. Duchier and R.J.Revillaud, Treatment of adult systemic mastocytosis with a Paf-acether antagonist BN 52063, Lancet II:114 (1988).CrossRefGoogle Scholar
  52. 52.
    K.B. Yancy, C.H. Hammer, L. Harveth, L. Renter, M.M. Frank and T.J. Lawley, Studies of human C5a as a mediator of inflammation in normal skin, J. clin. Invest. 75:486 (1985).CrossRefGoogle Scholar
  53. 53.
    H. Takematsu, K. Ohkohci and H. Tagami, Demonstration of anaphylatoxins C3a, C4a and C5a in the scales of psoriasis and inflammatory pustular dermatoses, Br. J. Dermatol. 114:1 (1986).PubMedCrossRefGoogle Scholar
  54. 54.
    J-M. Schroder and E. Christophers, Identification of C5a des arg and an anionic neutrophil-activating peptide (ANAP) in psoriatic scales, J. Invest. Dermatol. 87:53 (1986).PubMedCrossRefGoogle Scholar
  55. 55.
    J-M. Schroder and E. Christophers, Transient absence of C5a-specific neutrophil function in inflammatory disorders of the skin, J. Invest. Dermatol. 85:194 (1985).PubMedCrossRefGoogle Scholar
  56. 56.
    R.D.R. Camp, N.J. Fincham, F.M. Cunningham, M.W. Greaves, J. Morris and A. Chu, Psoriatic skin lesions contain biologically active amounts of an interleukin-1-like compound, J. Immunol. 137:3469 (1986).PubMedGoogle Scholar
  57. 57.
    G. Lisby, C. Avnstorp and G.L. Wantzin, Interleukin 1. A new mediator in Dermatology, Int. J. Dermatol. 26:8 (1987).PubMedCrossRefGoogle Scholar
  58. 58.
    T. Yoshimura, K. Matsushima, J.J. Oppenheim and E.J. Leonard, Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes. Partial characterisation and separation from interleukin 1 (IL-1), J. Immunol. 139:788 (1987).PubMedGoogle Scholar
  59. 59.
    J-M. Schroder, U. Mrowietz, E. Morita and E. Christophers, Purification and partial characterisation of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity, J. Immunol. 139:3474 (1987).PubMedGoogle Scholar
  60. 60.
    N.J. Fincham, R.D.R. Camp, A.J.H. Gearing, C.R. Bird and F.M. Cunningham, Neutrophil chemoattractant and IL-1-like activity in samples from psoriatic skin lesions, J. Immunol. 140:294 (1988).Google Scholar
  61. 61.
    R.D.R. Camp, F.M. Cunningham, N.J. Fincham, M.W. Greaves, A. Kobza Black, A.I. Mallet and P.M. Woollard, Psoriatic skin lesions contain a novel lipid neutrophil chemokinetic compound which is distinct from known chemoattractant compounds, Br. J. Pharmacol. 94:1043 (1988).PubMedGoogle Scholar
  62. 62.
    H. Takematsu, R. Suzuki, H. Tagami and K. Kumagai, Interleukin-1 like activity in horny layer extracts: Decreased activity in scale extracts of psoriasis and sterile pustular dermatoses, Dermatologica 172:236 (1986). PubMedCrossRefGoogle Scholar
  63. 63.
    . P.M. Dowd, R.D.R. Camp and M.W. Greaves, Human recombinant interleukin-1 α is proinflammatory in normal human skin, Skin Pharmacol. 1:30 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Fiona M. Cunningham
    • 1
  1. 1.Dept. of Veterinary Basic SciencesThe Royal Veterinary CollegeHertfordshireEngland

Personalised recommendations