Differential IL-10 receptor gene expression in acute versus chronic atopic eczema. Modulation by immunosuppressive drugs and cytokines in normal cultured keratinocytes.
OBJECTIVE
The effects of the anticytokine interleukin 10 (IL-10) are mediated by specific receptors. In this study we examined the role of the IL-10 receptor (IL-10R) in the pathophysiology of atopic eczema.


METHODS
For this purpose we analyzed the expression of IL-10R in the skin of patients with acute and chronic atopic eczema in comparison to the expression in healthy individuals using in situ binding experiments with fluorescently labeled IL-10 and semiquantitative reverse transcriptase-PCR specific for IL-10R1. In addition, we studied the influence of the Th2-associated cytokine interleukin-4 (IL-4), the Th1-associated gamma-interferon (IFN-gamma), the immunosuppressive drug FK506, the H1-antagonist loratadine and UVA irradiation on the expression of IL-10R1 in cultured normal human keratinocytes.


RESULTS
We found that IL-10 receptor mRNA and protein are strongly downregulated in acute phase atopic lesions. Furthermore we could show that IL-4, IFN-gamma, FK506, loratadine and UVA enhance the mRNA levels of the IL-10R1 in vitro in normal cultured keratinocytes. We could also demonstrate restored IL-10R1 mRNA levels in lesional atopic skin of a patient after UVA1 therapy.


CONCLUSIONS
Our results demonstrate for the first time that IL-10 receptors may have a role in the pathogenesis of atopic eczema and its upregulation by FK506 and UVA could explain the therapeutic efficacy of these agents.
Müschen
A
A
Department of Dermatology, Heinrich-Heine-University Düsseldorf, Germany.
Mirmohammadsadegh
A
A
Jarzebska-Deussen
B
B
Abts
H F
HF
Ruzicka
T
T
Michel
G
G
D000208:Acute Disease; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000503:physiopathology* / Q000532:radiotherapy; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018123:Receptors, Interleukin / Q000032:analysis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D053701:Receptors, Interleukin-10; D016559:Tacrolimus / Q000494:pharmacology; D014467:Ultraviolet Therapy
D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016559:Tacrolimus