Abstract
To explore the pruritogenic and inflammatory effects of cytokines, a single dose of 20 μg recombinant human interleukin-2 was injected intradermally into eight patients with atopic dermatitis and eight healthy controls. The study was double-blind and randomized with glucose as a negative control. The effects were evaluated by recording local itch and erythema over 72 h and by examining skin biopsies taken at 24 h and 72 h. In patients and controls, interleukin-2 provoked a low-intensity local itch with maximal intensity between 6 h and 48 h and erythema with maximal extension between 12 h and 72 h. In the atopic dermatitis patients, these reactions tended to appear earlier and were less pronounced than in the healthy controls. Interleukin-2 induced dermal mononuclear cell infiltrates consisting mainly of CD3+ cells. A majority of the T cells were CD4+. The number of dermal CD25+, HLA-DR+ and ICAM-1+ cells was also increased at the interleukin-2 injection sites. In the epidermis, interleukin-2 induced spongiosis and exocytosis as well as HLA-DR+ and ICAM-1+ keratinocytes. The microscopic findings tended to be more prominent at 72 h than at 24 h in both groups, but with a somewhat slower onset in the atopic dermatitis patients. In conclusion, a single intradermal injection of interleukin-2 induced local itch, erythema, dermal T-cell infiltrates, spongiosis, exocytosis and activation of keratinocytes both in atopic dermatits patients and in healthy controls.
Similar content being viewed by others
References
Arthur RP, Shelley WB (1959) The innervation of human epidermis. J Invest Dermatol 32: 397–411
Cooper KD (1991) Pathogenesis and pharmacology of atopic dermatitis. In: Czernielewski JM (ed) Immunological and pharmalogical aspects of atopic and contact eczema. Pharmacology and the skin. Karger, Basel, pp 119–127
Currie JM, Wright RC, Miller OG (1971) The frequency of warts in atopic patients. Cutis 8: 243–244
Davis MJ, Lawler JC (1958) Observations on the delayed blanch phenomenon in atopic subjects. J Invest Dermatol 30: 127–131
Del Prete G (1992) Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy. Allergy 47: 450–455
Del Prete G, Maggi E, Parronchi P, Chrétien I, Tiri A, Macchia D, Ricci M, Banchereau J, Vries de J, Romagnani S (1988) IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol 140: 4193–4198
Dowd PM, Camp RDR, Greaves MW (1988) Human recombinant interleukin-1α is proinflammatory in normal human skin. Skin Pharmacol 1: 30–37
Gaspari AA, Lotze MT, Rosenberg SA, Stern JB, Katz SI (1987) Dermatologic changes associated with interleukin 2 administration. JAMA 258: 1624–1629
Giannetti A, Girolomoni G (1989) Skin reactivity to neuropeptides in atopic dermatitis. Br J Dermatol 121: 681–688
Grewe M, Gyufko K, Schöpf E, Krutmann J (1994) Lesional expression of interferon-γ in atopic eczema. Lancet 343: 25–26
Handwerker HO, Magerl W, Klemm F, Lang E, Westerman RA (1987) Quantitative evaluation of itch sensation. In: Schmidt RF, Schaible HG, Wahle-Hinz C (eds) Fine afferent nerve fibers and pain. VCH Verlagsgesellschaft, Weinheim, pp 461–473
Handwerker HO, Forster C, Kirchhoff C (1991) Discharge patterns of human C-fibers induced by itching and burning stimuli. J Neurophysiol 66: 307–315
Hanifin JM (1990) Immunologic aspects of atopic dermatitis. Dermatol Clin 8: 747–750
Hanifin JM, Rajka G (1980) Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh) 92: 44–47
Hägermark Ö (1985) Pruritus. In: Fry L (ed) Skin problems in the elderly. Churchill Livingstone, Edinburgh London Melbourne, pp 267–292
Hägermark Ö (1989) Recent advances in the pathophysiology of itch. Allergologie 12: S139–142
Heijden FL van der, Wierenga EA, Bos JD, Kapsenberg ML (1991) High frequency of IL-4-producing CD4+ allergen-specific T lymphocytes in atopic dermatitis lesional skin. J Invest Dermatol 97: 389–394
Juhlin L (1961) Skin reactions to iontophoretically administered epinephrine and norepinephrine in atopic dermatitis. J Invest Dermatol 37: 201–205
Kaplan G, Kiessling R, Teklemariam S, Hancock G, Sheftel G, Job CK, Converse P, Ottenhoff THM, Becx-Bleumink M, Dietz M, Cohn ZA (1989) The reconstitution of cell-mediated immunity in the cutaneous lesions of lepromatous leprosy by recombinant interleukin 2. J Exp Med 169: 893–907
Leonard EJ, Yoshimura T, Tanaka S, Raffeld M (1991) Neutrophil recruitment by intradermally injected neutrophil attractant/activation protein-1. J Invest Dermatol 96: 690–694
Mihm MC, Soter NA, Dvorak HF, Austen KF (1976) The structure of normal skin and the morphology of atopic eczema. J Invest Dermatol 67: 305–312
Norris DA (1990) Cytokine modulation of adhesion molecules in the regulation of immunologic cytotoxicity of epidermal targets. J Invest Dermatol 95: 111S-120S
Palacios J, Fuller EW, Blaylock WK (1966) Immunological capabilities of patients with atopic dermatitis. J Invest Dermatol 47: 484–490
Rajka G (1989) Essential aspects of atopic dermatitis. Springer, Berlin Heidelberg New York
Ramb-Lindhauer C, Feldmann A, Rotte M, Neumann C (1991) Characterization of grass pollen reactive T-cell lines derived from lesional atopic skin. Arch Dermatol Res 283: 71–76
Reijsen FC van, Bruijnzeel-Koomen CAFM, Kalthoff FS, Maggi E, Romagnani S, Westland JKT, Mudde GC (1992) Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients with atopic dermatitis. J Allergy Clin Immunol 90: 184–193
Reinhold U, Kukel S, Goeden P, Neumann U, Wehrmann W, Kreysel HW (1991) Interleukin-4 promotes the expansion of skin-infiltrating lymphocytes from atopic dermatitis in vitro. J Invest Dermatol 96: 370–375
Romagnani S (1992) Induction of TH1 and TH2 responses: a key role for the “natural” immune response? Immunol Today 13: 379–381
Romagnani S, Maggi E, Del Prete GF, Parronchi P, Macchia D, Tiri A, Ricci M (1989) Role of interleukin 4 and gamma interferon in the regulation of human IgE synthesis: possible alterations in atopic patients. Int Arch Allergy Appl Immunol 88: 111–113
Romeis B (1948) Mikroskopische Teknik. Leibniz, München
Ryan TJ (1991) Vascular reactivity in atopic eczema. In: Ruzicka T, Ring J, Przybilla B (eds) Handbook of atopic eczema. Springer, Berlin Heidelberg New York, pp 263–277
Rystedt I, Strannegård IL, Strannegård Ô (1986) Recurrent viral infections in patients with past or present atopic dermatitis. Br J Dermatol 114: 575–582
Solomon LM, Wentzel HE, Tulsky E (1964) The physiological disposition of C14-norepinephrine in patients with atopic dermatitis and other dermatoses. J Invest Dermatol 43: 193–200
Sternberger LA (1979) Immunocytochemistry. John Wiley & Sons, New York
Tai PC, Spry CJF, Peterson C, Venge P, Olsson I (1984) Monoclonal antibodies distinguish between storage and secreted forms of eosinophil cationic protein. Nature 309: 182–184
Vercelli D, Jabara HH, Lauener RP, Geha RS (1990) IL-4 inhibits the synthesis of IFN-γ and induces the synthesis of IgE in human mixed lymphocyte cultures. J Immunol 144: 570–573
Wahlgren CF (1991) Itch and atopic dermatitis: clinical and experimental studies. Acta Derm Venereol Suppl (Stockh) 165: 1–53
Wahlgren CF (1992) Pathophysiology of itching in urticaria and atopic dermatitis. Allergy 47: 65–75
Wahlgren CF, Hägermark Ö, Bergström R (1991) Patients' perception of itch induced by histamine, compound 48/80 and wool fibres in atopic dermatitis. Acta Derm Venereol (Stockh) 71: 488–494
Wahlgren CF, Scheynius A, Hägermark Ö (1990) Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta Derm Venereol (Stockh) 70: 323–329
Zachary CB, MacDonald DM (1983) Quantitative analysis of T-lymphocyte subsets in atopic eczema, using monoclonal antibodies and flow cytofluorimetry. Br J Dermatol 108: 411–422
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wahlgren, C.F., Hägermark, Ö., Linder, M.T. et al. Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects. Arch Dermatol Res 287, 572–580 (1995). https://doi.org/10.1007/BF00374079
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00374079