Interleukin 6 is Expressed in High Levels in Psoriatic Skin and Stimulates Proliferation of Cultured Human Keratinocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 16; pp. 6367 - 6371
• Main Authors: Grossman, Rachel M., Krueger, James, Yourish, Debra, Granelli-Piperno, Angela, Murphy, Daniel P., May, Lester T., Kupper, Thomas S., Sehgal, Pravinkumar B., Gottlieb, Alice B.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1989; National Acad Sciences
• Subjects: Antibodies; Biological and medical sciences; Cell Division - drug effects; Cell growth; Cells, Cultured; Cytokines; Dermatology; Endothelial cells; Epidermal Cells; Epidermis - drug effects; Fluorescent Antibody Technique; Humans; Hyperplasia; Immunoenzyme Techniques; Interleukin-6; Interleukins - biosynthesis; Interleukins - genetics; Interleukins - pharmacology; Keratinocytes; Keratins - analysis; Medical sciences; Messenger RNA; Nucleic Acid Hybridization; Psoriasis; Psoriasis - metabolism; Psoriasis - pathology; Psoriasis. Parapsoriasis. Lichen; Recombinant Proteins - pharmacology; RNA, Messenger - analysis; RNA, Messenger - genetics; Skin; Skin - metabolism; Skin - pathology; Transcription, Genetic; Ungulates; Human; Interleukin 6; Cell culture; Keratinocyte; Skin disease; Psoriasis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.16.6367

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.