Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects

Abstract

To explore the pruritogenic and inflammatory effects of cytokines, a single dose of 20 micrograms 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 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 dermatitis patients and in healthy controls.

Uremic Pruritus – An Update

“…IL-2, when given intravenously as a part of cancer therapy, causes erythema and itching [55]. Intradermal injection of IL-2 leads to intense pruritus [56].…”

Role of Antigen-Induced Cytokine Release in Atopic Pruritus

“…Since the timing as well as the quantity of secreted cytokines tested here fail to correlate with the skin test reactivity in the patients, one must postulate that cytokines other than those examined so far are responsible for the whealing and itching. Of the cytokines known until now, itching has been reported for IL-2 and GM-CSF only after local and systemic application [3, 4, 5]. These molecules can be excluded as possible candidates to explain the skin test reactions, on the basis of the present data.…”

“…While pruritus can be induced by a number of mediators other than histamine, including mast cell proteases and neurotransmitters [2], cytokines are increasingly implicated as possible causative agents. Evidence for this is based on the response of atopic itching to corticosteroids and cyclosporin, on the pronounced involvement of cytokine-producing leukocytes in atopic inflammation, and on the induction of itching by selected cytokines like GM-CSF and interleukin-2 (IL-2) during human clinical studies [3, 4, 5]. …”

TRP Channels and Pruritus

“…For example, IL-2 was found to induce itch [135,136] and to activate a histamine and bradykinin sensitive subpopulation of sensory C-fibers [137,138]. Interestingly, bradykinin potentiated the chemo-responsiveness of polymodal nociceptors to IL-2 [139] resulting in a bi-directional augmentation.…”