The treatment of psoriasis with IL-10: rationale and review of the first clinical trials.
By virtue of its anti-inflammatory and immunosuppressive properties, IL-10 plays a crucial role in several immune reactions, including regulatory mechanisms in the skin. In psoriasis, a common cutaneous immune disease, a relative deficiency in cutaneous IL-10 expression is observed. Several lines of evidence suggest that IL-10 could have antipsoriatic abilities. One pilot and two Phase II trials with sc. IL-10 administration over 3 - 7 weeks in patients with moderate to severe psoriasis have supported this hypothesis. The therapy was well-tolerated and clinical efficiency was found in the majority of patients. Immunosuppressive effects (depressed monocytic HLA-DR expression, TNF-alpha and IL-12 secretion capacity, IL-12 plasma levels and responsiveness to recall antigens) as well as a shift towards a Type 2 cytokine pattern (increasing proportion of IL-4, IL-5, and IL-10 producing T-cells, selective increase in IgE serum levels) were observed. These investigations suggest that IL-10 is of major importance in psoriasis and show that IL-10 administration represents a new therapeutic approach. However, long-term administration of large recombinant protein limits the value of this novel therapeutic approach. As such, neither oral nor topical applications are possible; there is a risk of the development of neutralising antibodies.
Asadullah
K
K
Experimental Dermatology, Schering AG, D-13342 Berlin, Germany.
Döcke
W D
WD
Sabat
R V
RV
Volk
H D
HD
Sterry
W
W
D002986:Clinical Trials as Topic; D003879:Dermatologic Agents / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000502:physiology / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use
D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D016753:Interleukin-10