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Altered cytokine production in black patients with keloids

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Abstract

The treatment of keloids in black patients remains a medical dilemma. Previous studies have focused on primary alterations in the metabolism of fibroblasts as the key in the etiology of this condition. Yet alterations in the production of various cytokines which may alter fibroblast responses secondarily have received little attention. Twelve black patients with clinical and histological diagnosis of keloids and eight black control volunteers were studied. Peripheral blood mononuclear-cell (PBMC) fractions from both groups were assayed for production of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), alpha-interferon (IFN-α), beta-interferon (IFN-β), gamma-interferon (IFN-γ), tumor necrosis factor-alpha (TNF-α), and tumor necrosis factor-beta (TNF-β). The production of IFN-α, IFN-γ, and TNF-β were markedly depressed in keloid patients compared to normal controls. However, IL-1 and IL-2 production was not significantly different between the two groups. In contradistinction, keloid patients produce greater amounts of IL-6, TNF-α, and IFN-β. Altered levels of immunoregulatory cytokines may play a significant role in the net increase in collagen which characterizes keloid formation.

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References

  1. Cosman B, Crikelair GF, Ju DMC, Gaulin JC, Lattes R: Surgical management of keloids. Plastic Reconstruct Surg 27:335–345, 1961

    Google Scholar 

  2. Peacock EE, Madden JW, Trier WC: Biological basis of treatment of keloids and hypertrophic scars. South Med J 63:755–760, 1970

    PubMed  Google Scholar 

  3. Murray JC, Pollack SV, Pinnell SR: Keloids: A review. J Am Acad Dermatol 4:461–470, 1981

    PubMed  Google Scholar 

  4. Ketchum LD: Hypertrophic scars and keloids. Clin Plast Surg 4:301–310, 1977

    PubMed  Google Scholar 

  5. Olumasanmi JO: Keloids in the African. Clin Plast Surg 1:179–195, 1974

    PubMed  Google Scholar 

  6. Kamin AJ: The etiology of keloids. A review of the literature and a new hypothesis. S Afr Med J 38:913–916, 1974

    Google Scholar 

  7. Omo-Dare P: Genetic studies in keloid. J Natl Med Assoc 67:428–432, 1975

    PubMed  Google Scholar 

  8. Bloom D: Heredity of keloids. A review of the literature and a report of a family with multiple keloids in five generations. NY State J Med 56:511–519, 1956

    Google Scholar 

  9. Russell JP, Witt WS: Cell size and growth characteristics of cultured fibroblasts isolated from normal and keloid tissue. Plastic Reconstruct Surg 57:207–212, 1976

    Google Scholar 

  10. Diegelman RF, Cohen IK, McCoy BJ: Growth kinetics and collagen synthesis in normal skin, normal scar and keloid fibroblasts in-vitro. J Cell Physiol 98:341–346, 1979

    PubMed  Google Scholar 

  11. Craig RDP, Schofield JD, Jackson JS: Collagen biosynthesis in normal skin, normal and hypertrophic scar and keloid. Eur J Clin Invest 5:69–72, 1975

    PubMed  Google Scholar 

  12. Elias JA, Rossman MD, Daniek RP: Inhibition of human lung fibroblast growth by mononuclear cells. Am Rev Resp Dis 125:701–705, 1982

    PubMed  Google Scholar 

  13. Wahl SM, Wahl LM, McCarthy JB: Lymphocyte mediated activation of fibroblast proliferation and collagen production. J Immunol 121:942–946, 1978

    PubMed  Google Scholar 

  14. Diegelman RF, Cohen IK: Modulation of fibroblast DNA synthesis by macrophages. Plast Surg Forum 2:167, 1977

    Google Scholar 

  15. Stuart J, Postlethwaite AE, Kang AH: Evidence of cell mediated immunity to collagen in progressive systemic sclerosis. J Lab Clin Med 88:601–605, 1976

    PubMed  Google Scholar 

  16. Kravis TC, Ahmed A, Brown TE, Fulmer JD, Crystal RG: Pathogenic mechanisms in pulmonary fibrosis. Collagen induced migration inhibition factor production and cytotoxicity mediated by lymphocytes. J Clin Invest 58:1223–1232, 1976

    PubMed  Google Scholar 

  17. Langford MP, Stanton GJ, Johnson HM: Biological effects of staphylococcal entertoxin A on human peripheral lymphocytes. Infect Immun 22:62–68, 1978

    PubMed  Google Scholar 

  18. Wironowska-Stewart M, Stewart WE II: Determination of human leukocyte populations involved in production of interferon alpha and gamma. J IFN Res 1:233–243, 1981

    Google Scholar 

  19. Blyden G, Handschumacher RE: Purification and properties of human lymphocyte activating factor (LAF). J Immunol 118:1631–1638, 1977

    PubMed  Google Scholar 

  20. Gillis S, Ferm M, On W,et al.: T-cell growth factor: Parameters of production and quantitative microassay for activity. J Immunol 120:2027–2032, 1978

    PubMed  Google Scholar 

  21. Flick DA, Gifford GE: Comparison of in-vitro cell cytotoxicity assay for tumor necrosis factor. J Immunol Methods 68:167–175, 1984

    PubMed  Google Scholar 

  22. Neilson EG, Jimenez SD, Phillips MS: Cell mediated immunity in interstitial nephritis. T-lymphocyte mediated fibroblast proliferation and collagen synthesis: An immune mechanism for renal fibrogenesis. J Immunol 125:1708–1714, 1980

    PubMed  Google Scholar 

  23. Chopra V, Tyring SK, Johnson L, Fine JD: Patients with severe forms of inherited epidermolysis bullosa exhibit decreased lymphokine and monokine production. J Clin Immunol 10:321–329, 1990

    PubMed  Google Scholar 

  24. Reed WB, College J, Francese MJO: Epidermolysis bullose dystrophica with epidermal neoplasma. Arch Dermatol 110:894–902, 1974

    PubMed  Google Scholar 

  25. Nooze M, Dennis M, Hennan J: Modulation of human lymphocyte response by cartilage proteoglycan and glycoaminoglycans: A comparison between normal subjects and patients with rheumatoid arthritis. Clin Immunol Pathol 12:369–381, 1979

    Google Scholar 

  26. Clark JG, Kostal KM, Marino BA: Bleonycin-induced pulmonary fibrosis in hamsters. J Clin Invest 72:2082–2091, 1983

    PubMed  Google Scholar 

  27. Huybrechts-Godin G, Peeters-Jovis C, Vaes G: Partial characterization of the macrophage factor that stimulates fibroblasts to produce collagenase and to degrade collagen. Biochim Biophys Acta 846:51–54, 1985

    PubMed  Google Scholar 

  28. DeLustro FG, Sherer GK, LeRoy EC: Human monocyte stimulation of fibroblast growth by a soluble mediator(s). J Reticuloendothel Soc 28:519–532, 1988

    Google Scholar 

  29. Dayer JM, Goldring SR, Robinson DR, Krane SM: Effects of human mononuclear cells factor on cultured rheumatoid synovial cells. Biochimice Biophys Acta 586:87–105, 1979

    Google Scholar 

  30. Korn JH, Halushka PV, LeRoy EC: Mononuclear cell modulation of connective tissue function: Suppression of fibroblast growth by stimulation of exogenous prostaglandin production. J Clin Invest 65:543–554, 1980

    PubMed  Google Scholar 

  31. Jimenez SD, McArthur W, Rosenbloom J: Inhibition of collagen synthesis by mononuclear cell supernatant. J Exp Med 1421–1431, 1979

  32. Turk CW, Dohlman JE, Goetzl EJ: Immunologic mediators or wound healing. J Cell Physiol 5:89–93, 1987

    Google Scholar 

  33. Jimenez SA, Freundlich B, Rosenbloom J: Selective inhibition of human diploid fibroblast collagen synthesis by interferons. J Clin Invest 74:1112–1116, 1984

    PubMed  Google Scholar 

  34. Duncan MR, Berman B: γ-Interferon is the lymphokine and β-interferon is the monokine responsible for inhibition of fibroblast collagen production and later but not early fibroblast proliferation. J Exp Med 162:516–527, 1985

    PubMed  Google Scholar 

  35. Elias JA, Jimenez SA, Freundlich B: Recombinant gamma, alpha and beta interferon regulation by lung fibroblast proliferation. Am Rev Resp Dis 135:62–65, 1987

    PubMed  Google Scholar 

  36. Berman B, Duncan MR: Short term keloid treatment in vivo with human interferon alpha-2b results in a selective and persistant normalization of keloidal collagen, glycosaminoglycan and collagen production in vitro. J Am Acad Dermatol 21:694–702, 1989

    PubMed  Google Scholar 

  37. Larrabee WI, East CA, Jafee HS, Stephenson C, Peterson KE: Intralesional interferon gamma treatment for keloids and hypertrophic scars. Arch Otolaryngol Head Neck Surg 116:1159–1162, 1990

    PubMed  Google Scholar 

  38. Abdullah A, McCauley RL, Herndon DN: Stimulation of human dermal fibroblasts with interleukin-2. J Burn Care Rehab 12:23–25, 1991

    Google Scholar 

  39. Dayer JM, de Rochemonteix B, Burrius B, Demczaks S, Dinerello CA: Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J Clin Invest 77:645–648, 1986

    PubMed  Google Scholar 

  40. Schmidt JA, Mizel SB, Cohen S, Green I: Interleukin I: A potent regulator of fibroblast proliferation. J Immunol 128:2177–2182, 1982

    PubMed  Google Scholar 

  41. Zucali JR, Dinarello CA, Oblon DJ, Gross MA, Anderson L, Weinon RS: Interleukin I stimulates fibroblast to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest 77:1857–1863, 1986

    PubMed  Google Scholar 

  42. Meyer FA, Yaron I, Yaron M: Synergistic, additive and antagonistic effects of interleukin-1β, tumor necrosis factor-α and γ-interferon on prostaglandin E, hyaluronic acid and collagenase production by cultured synovial fibroblasts. Arth Rheum 33:1518–1525, 1990

    Google Scholar 

  43. VanDamme J, Opdenakker G: Interactions of interferons with skin reactive cytokines: From interleukin 1 to interleukin 8. J Invest Dermatol Suppl 95(6):905–935, 1990

    Google Scholar 

  44. Duncan MR, Berman B: Differential regulation of collagen, glycosaminoglycan, and collagenase activity production in cultured human dermal fibroblasts by interleukin 1-alpha and beta and tumor necrosis factor alpha and beta. J Invest Dermatol 92:699–706, 1989

    PubMed  Google Scholar 

  45. Katz Y, Strunk RC: Interleukin 1 and tumor necrosis factor: Similarities and differences in stimulation of expression of alternate pathway of complement and IFN-β2/IL-6 genes in human fibroblasts. J Immunol 42:3862–3867, 1989

    Google Scholar 

  46. Kohase M, Hendrickson-DeStefano D, May LT, Vilcek J, Sehgal PB: Induction of β2 interferon by tumor necrosis factor: A homeostatic mechanism in the control of cell proliferation. Cell 45:659–666, 1986

    PubMed  Google Scholar 

  47. VanDamme J, Schaafsna RM, Fibbe WE, Falkenberg JHF, Opdenakkar G, Billian A: Simultaneous production of interleukin-6, interferon-β and colony stimulating activity by fibroblasts after viral and bacterial infection. Eur J Immunol 19:163–168, 1989

    PubMed  Google Scholar 

  48. Neuner P, Urbani A, Trautinger F, Moler A, Kirnbauer R, Kapp A, Schopf E, Schwarz T, Lugar TA: Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis. J Invest Dermatol 97:27–33, 1991

    PubMed  Google Scholar 

  49. Bhardway N, Santhanam V, Law LL, Tatter SB, Ghrayeb J, Rivelis M, Steinman RM, Sehgal PB, May LT: IL-6/IFN-β2 in synovial effusions of some patients with rheumatoid arthritis and other arthritises. J Immunol 143:2153–2159, 1989

    PubMed  Google Scholar 

  50. Helfgott DC, Tatter SD, Santhanam V, Clarick RH, Bardway N, May LT, Sehgal PB: Interferon β2/Interleukin-6 in plasma and body fluid during acute bacterial infection. J Immunol 142:948–953, 1989

    PubMed  Google Scholar 

  51. Carswell EA, Old LJ, Kassel L, Green S, Fiore N, Williamson B: An endotoxin induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666–3670, 1975

    PubMed  Google Scholar 

  52. Gery I, Waksman BH: Potientation of the T-lymphocyte response to mitogens. J Exp Med 136:143–155, 1972

    PubMed  Google Scholar 

  53. Ramamurthy V, Fleishmann NR: Regulation of IFN-β activity by fibroblasts. Antivir Res 6:267–275, 1986

    PubMed  Google Scholar 

  54. Gastl G, Huber C: The biology of interferon actions. Blut 56:193–199, 1988

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Skin Tissue Culture Laboratory of the Shriners Burns Institute, 77550, Galveston, Texas

    Robert L. McCauley, Vimlarani Chopra & Ying-Yue Li

  2. Division of General Surgery, Department of Surgery, University of Texas Medical Branch, 77550, Galveston, Texas

    David N. Herndon

  3. Division of Plastic Surgery, Department of Surgery, University of Texas Medical Branch, 77550, Galveston, Texas

    Robert L. McCauley & Martin C. Robson

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  1. Robert L. McCauley
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  2. Vimlarani Chopra
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  3. Ying-Yue Li
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  4. David N. Herndon
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  5. Martin C. Robson
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McCauley, R.L., Chopra, V., Li, YY. et al. Altered cytokine production in black patients with keloids. J Clin Immunol 12, 300–308 (1992). https://doi.org/10.1007/BF00918154

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