Epidermal Cytokines IL-1β, TNF-α, and IL-12 in Patients with Atopic Dermatitis: Response to Application of House Dust Mite Antigens11This work is published in part as an abstract inArch Dermatol Res 1997, 289 (Suppl.): A45

Abstract

Epidermal cytokines such as interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-12 have been described to play a crucial role in the induction and elicitation phase of allergic contact dermatitis upon exposure to haptens. In this study we asked whether these cytokines may also play a role in the epidermis of patients with atopic dermatitis after the application of house dust mite antigens (HDM) to their skin. Epidermal samples were collected by scraping healthy appearing skin of atopic patients and healthy individuals 8 h after the application of an extract of HDM. Sodium lauryl sulfate and saline served as controls. Reverse transcriptase-polymerase chain reaction was performed for IL-1beta, tumor necrosis factor-alpha, IL-12 p35, and IL-12 p40. Exposure to HDM led to a significant upregulation of mRNA of these cytokines in atopic patients only. Whereas IL-1beta and tumor necrosis factor-alpha also showed an upregulation in part of these patients after exposure to the irritant sodium lauryl sulfate, IL-12 p40 mRNA was exclusively enhanced by the application of the allergen. In contrast to IL-12 p40, IL-12 p35 mRNA was not detectable in significant amounts. Interestingly, also in untreated, normal appearing skin of atopic individuals (n = 16), the levels of these cytokines were higher than in normal individuals (n = 8), possibly explaining the increased skin irritability of atopic individuals. Finally, comparing epidermal cytokines in the skin of patients who developed a positive allergen patch test to those who stayed negative, suggests that only expression of IL-1beta mRNA may be a predictive marker for the development of a positive patch test reaction to HDM.

FcεRI engagement of Langerhans cell–like dendritic cells and inflammatory dendritic epidermal cell–like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro☆

“…Allergen presentation by epidermal LCs from patients with AD to T cells has been shown to be mediated through allergen-specific IgE molecules in previous studies. 24 Furthermore, the capacity of IDEC-DCs to release both cytokines IL-12 and IL-18 in high amounts after FceRI cross-linking or after activation with proinflammatory stimuli, such as LPS, sustains the development of an immune reaction of the T H 1 type. 25 In this way IDECs might contribute to the switch from the initial phase of AD into the IFN-c-predominant chronic eczematous phase.…”

“…29 In addition, a profound decrease of IL-12 could be observed in the successfully treated skin of patients with AD. 24,30,31 Because keratinocytes coexpress IL-18 at the mRNA level, as well as at the protein level, they might represent an important additional source of IL-12 and IL-18 in vivo. 32 In contrast to recent concepts explaining the polarization process of DCs, both LC and IDEC subtypes develop from the same precursor monocyte, and the influence of additional soluble and membrane-bound signals leads to the outcome of the T H 1 or T H 2 cytokine response of T cells.…”

Infliximab in the treatment of moderate to severe atopic dermatitis

“…Patients with AD reportedly have significantly elevated serum and tissue concentrations of TNF-a and, thus, may be responsive to treatment with TNF-ainhibitors. 1,4,5 Infliximab is a chimeric monoclonal antibody that consists of a murine F ab -portion specific for human TNF-a and the constant region (F c ) of human IgG 1 . Infliximab binds with high specificity and affinity to free and membrane-bound TNF-a.…”

Glucocorticoids for Human Skin: New Aspects of the Mechanism of Action

“…Consequently, alveolar macrophages of asthma patients and keratinocytes of patients with atopic dermatitis release interleukin-1 (IL-1), tumour necrosis factor-␣ (TNF-␣ ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at an increased rate [21,[23][24][25] . By stimulating cytokine receptors on the cell surface, IL-1 and TNF-␣ induce a cellular signal cascade which activates transcription factors such as signal transducers and activators of transduction (STATs) or the nuclear factor B (NF-B) which is released from the complex with its inhibitory protein I B ␣ .…”