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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Aug;86(16):6367–6371. doi: 10.1073/pnas.86.16.6367

Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes.

R M Grossman 1, J Krueger 1, D Yourish 1, A Granelli-Piperno 1, D P Murphy 1, L T May 1, T S Kupper 1, P B Sehgal 1, A B Gottlieb 1
PMCID: PMC297840  PMID: 2474833

Abstract

Psoriasis is a common papulosquamous skin disease. The histopathology is characterized by epidermal hyperplasia and inflammation. Recent studies suggest that keratinocyte proliferation and inflammation in psoriasis are manifestations of the same underlying pathological process. Interleukin 6 (IL-6), a cytokine that is a major mediator of the host response to tissue injury and infection, is produced by both keratinocytes and leukocytes in culture. IL-6 expression was studied in psoriatic plaques by immunoperoxidase staining with two different polyclonal anti-recombinant IL-6 antisera and by in situ nucleic acid hybridization with IL-6 cRNA probes. Epidermal and dermal cells in active psoriatic plaques from 35 psoriasis patients stained heavily for IL-6 as compared with nonlesional skin and with plaques after treatment with antimetabolic and antiinflammatory agents. Absorption of the anti-recombinant IL-6 antisera with purified fibroblast-derived IL-6 or with recombinant IL-6, but not bovine serum albumin, removed the immunostaining. Increased levels of IL-6 were detected in the plasma of patients with active psoriasis (mean 3 ng/ml) by using two different bioassays. IL-6 production by proliferating keratinocytes was suggested by IL-6-specific immunostaining in cultured normal and psoriatic keratinocytes and by the detection of mRNA specific for IL-6 in psoriatic epidermis by in situ hybridization. IL-6 stimulated the proliferation of cultured, normal human keratinocytes as assessed by two different assays. Thus, IL-6 could directly contribute to the epidermal hyperplasia seen in psoriatic epithelium as well as affect the function of dermal inflammatory cells.

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Selected References

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  1. Baker B. S., Swain A. F., Fry L., Valdimarsson H. Epidermal T lymphocytes and HLA-DR expression in psoriasis. Br J Dermatol. 1984 May;110(5):555–564. doi: 10.1111/j.1365-2133.1984.tb04678.x. [DOI] [PubMed] [Google Scholar]
  2. Coffey R. J., Jr, Derynck R., Wilcox J. N., Bringman T. S., Goustin A. S., Moses H. L., Pittelkow M. R. Production and auto-induction of transforming growth factor-alpha in human keratinocytes. 1987 Aug 27-Sep 2Nature. 328(6133):817–820. doi: 10.1038/328817a0. [DOI] [PubMed] [Google Scholar]
  3. Elder J. T., Fisher G. J., Lindquist P. B., Bennett G. L., Pittelkow M. R., Coffey R. J., Jr, Ellingsworth L., Derynck R., Voorhees J. J. Overexpression of transforming growth factor alpha in psoriatic epidermis. Science. 1989 Feb 10;243(4892):811–814. doi: 10.1126/science.2916128. [DOI] [PubMed] [Google Scholar]
  4. Falanga V., Zitelli J. A., Eaglstein W. H. Wound healing. J Am Acad Dermatol. 1988 Sep;19(3):559–563. doi: 10.1016/s0190-9622(88)80317-7. [DOI] [PubMed] [Google Scholar]
  5. Fong Y., Moldawer L. L., Marano M., Wei H., Tatter S. B., Clarick R. H., Santhanam U., Sherris D., May L. T., Sehgal P. B. Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man. J Immunol. 1989 Apr 1;142(7):2321–2324. [PubMed] [Google Scholar]
  6. Ganapathi M. K., May L. T., Schultz D., Brabenec A., Weinstein J., Sehgal P. B., Kushner I. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines. Biochem Biophys Res Commun. 1988 Nov 30;157(1):271–277. doi: 10.1016/s0006-291x(88)80043-3. [DOI] [PubMed] [Google Scholar]
  7. Gottlieb A. B., Chang C. K., Posnett D. N., Fanelli B., Tam J. P. Detection of transforming growth factor alpha in normal, malignant, and hyperproliferative human keratinocytes. J Exp Med. 1988 Feb 1;167(2):670–675. doi: 10.1084/jem.167.2.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gottlieb A. B. Immunologic mechanisms in psoriasis. J Am Acad Dermatol. 1988 Jun;18(6):1376–1380. doi: 10.1016/s0190-9622(88)70145-0. [DOI] [PubMed] [Google Scholar]
  9. Gottlieb A. B., Lifshitz B., Fu S. M., Staiano-Coico L., Wang C. Y., Carter D. M. Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques. J Exp Med. 1986 Oct 1;164(4):1013–1028. doi: 10.1084/jem.164.4.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gottlieb A. B., Luster A. D., Posnett D. N., Carter D. M. Detection of a gamma interferon-induced protein IP-10 in psoriatic plaques. J Exp Med. 1988 Sep 1;168(3):941–948. doi: 10.1084/jem.168.3.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Granelli-Piperno A. In situ hybridization for interleukin 2 and interleukin 2 receptor mRNA in T cells activated in the presence or absence of cyclosporin A. J Exp Med. 1988 Nov 1;168(5):1649–1658. doi: 10.1084/jem.168.5.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Helfgott D. C., Tatter S. B., Santhanam U., Clarick R. H., Bhardwaj N., May L. T., Sehgal P. B. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989 Feb 1;142(3):948–953. [PubMed] [Google Scholar]
  13. Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6;324(6092):73–76. doi: 10.1038/324073a0. [DOI] [PubMed] [Google Scholar]
  14. Kaplan G., Witmer M. D., Nath I., Steinman R. M., Laal S., Prasad H. K., Sarno E. N., Elvers U., Cohn Z. A. Influence of delayed immune reactions on human epidermal keratinocytes. Proc Natl Acad Sci U S A. 1986 May;83(10):3469–3473. doi: 10.1073/pnas.83.10.3469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kupper T. S. Interleukin 1 and other human keratinocyte cytokines: molecular and functional characterization. Adv Dermatol. 1988;3:293–307. [PubMed] [Google Scholar]
  16. Kupper T. S., Min K., Sehgal P., Mizutani H., Birchall N., Ray A., May L. Production of IL-6 by keratinocytes. Implications for epidermal inflammation and immunity. Ann N Y Acad Sci. 1989;557:454–465. [PubMed] [Google Scholar]
  17. Mansbridge J. N., Knapp A. M. Changes in keratinocyte maturation during wound healing. J Invest Dermatol. 1987 Sep;89(3):253–263. doi: 10.1111/1523-1747.ep12471216. [DOI] [PubMed] [Google Scholar]
  18. May L. T., Ghrayeb J., Santhanam U., Tatter S. B., Sthoeger Z., Helfgott D. C., Chiorazzi N., Grieninger G., Sehgal P. B. Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes. J Biol Chem. 1988 Jun 5;263(16):7760–7766. [PubMed] [Google Scholar]
  19. Ray A., Tatter S. B., May L. T., Sehgal P. B. Activation of the human "beta 2-interferon/hepatocyte-stimulating factor/interleukin 6" promoter by cytokines, viruses, and second messenger agonists. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6701–6705. doi: 10.1073/pnas.85.18.6701. [DOI] [PMC free article] [PubMed] [Google Scholar]

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