Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings.
Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase-polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards a type 2 cytokine pattern. The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10.
Asadullah
K
K
Institute of Medical Immunology and Department of Dermatology, University Hospital Charité, Berlin Humboldt University, Berlin, Germany. khusru.asadullah@schering.de
Friedrich
M
M
Hanneken
S
S
Rohrbach
C
C
Audring
H
H
Vergopoulos
A
A
Ebeling
M
M
Döcke
W D
WD
Volk
H D
HD
Sterry
W
W
D000328:Adult; D016207:Cytokines / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000627:therapeutic use*; D008967:Molecular Biology / Q000379:methods; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10