Document Detail


Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions.
MedLine Citation:
PMID:  10587516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from skin infiltration by type I T lymphocytes and release of associated cytokines. A multifunctional cytokine, rhIL-11, modulates macrophage and type I T-lymphocyte function in cell culture and shows anti-inflammatory activity in animal models. We are testing subcutaneous delivery of rhIL-11 to patients with psoriasis in a phase 1 open-label dose-escalation clinical trial. Tissue was obtained from lesional and uninvolved skin before and during treatment with rhIL-11 and was examined by histology/immunohistochemistry and quantitative RT-PCR. Expression of over 35 genes was examined in all patients, and multiple genetic markers of psoriasis were identified. Expression of numerous proinflammatory genes was elevated in psoriatic tissue compared with nonlesional skin. Seven of 12 patients responded well to rhIL-11 treatment. Amelioration of disease by rhIL-11, as shown by reduced keratinocyte proliferation and cutaneous inflammation, was associated with decreased expression of products of disease-related genes, including K16, iNOS, IFN-gamma, IL-8, IL-12, TNF-alpha, IL-1beta, and CD8, and with increased expression of endogenous IL-11. We believe that this is the first study in humans to indicate that type I cytokines can be selectively suppressed by an exogenous immune-modifying therapy. The study highlights the utility of pharmacogenomic monitoring to track patient responsiveness and to elucidate anti-inflammatory mechanisms.
Authors:
W L Trepicchio; M Ozawa; I B Walters; T Kikuchi; P Gilleaudeau; J L Bliss; U Schwertschlag; A J Dorner; J G Krueger
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  104     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-04     Completed Date:  2000-01-04     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1527-37     Citation Subset:  AIM; IM    
Affiliation:
Department of Molecular Medicine, Genetics Institute, Cambridge, Massachusetts 01810, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Surface / analysis
Cytokines / metabolism
Down-Regulation
Gene Expression Regulation / drug effects
Genetic Markers
Humans
Immunohistochemistry
Inflammation / drug therapy,  immunology
Injections, Subcutaneous
Interleukin-11 / therapeutic use*
Keratinocytes / drug effects
Leukocytes / drug effects,  immunology
Psoriasis / drug therapy*,  immunology
RNA, Messenger / metabolism
Recombinant Proteins / therapeutic use
Reverse Transcriptase Polymerase Chain Reaction
Skin / drug effects,  pathology
Time Factors
Grant Support
ID/Acronym/Agency:
AI-39214/AI/NIAID NIH HHS; GM-42461/GM/NIGMS NIH HHS; MO1-RR-00102/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Surface; 0/Cytokines; 0/Genetic Markers; 0/Interleukin-11; 0/RNA, Messenger; 0/Recombinant Proteins
Comments/Corrections
Erratum In:
J Clin Invest 2000 Feb;105(3):396

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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