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Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats.

Authors: Case, JP  Lorberboum-Galski, H  Lafyatis, R  FitzGerald, D  Wilder, RL  Pastan, I 
Citation: Case JP, etal., Proc Natl Acad Sci U S A. 1989 Jan;86(1):287-91.
Pubmed: (View Article at PubMed) PMID:2492102

Adjuvant arthritis in rats is a T-cell dependent "autoimmune" disease with close similarities to several forms of human arthritis. Injection of mycobacterial adjuvant leads to T-cell activation and proliferation, processes in which the de novo expression of the interleukin 2 (IL-2) receptor plays a pivotal role. The subsequent massive mononuclear cell infiltration of the joints ultimately results in complete joint destruction. Because activation of the helper/inducer subset of T lymphocytes is critical to the establishment of disease, we reasoned that IL2-PE40, a cytotoxic IL-2-Pseudomonas exotoxin fusion protein that targets the membrane-penetration and ADP-ribosylation domains of the toxin to cells bearing the IL-2 receptor, would be an effective and specific therapy. Adjuvant-injected rats were randomized to treatment with IL2-PE40, phosphate-buffered saline, or either of two control proteins related to IL2-PE40 but lacking either the receptor-binding moiety or an enzymatically active toxin domain and previously demonstrated to lack cytotoxicity in vitro. Intraperitoneal IL2-PE40 given before the establishment of overt clinical disease proved an effective and specific modifier of adjuvant arthritis by clinical, histological, and radiographic criteria. Our data suggest that IL2-PE40 may be effective in those diseases in which activated T-cells play an important role.

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CRRD Object Information
CRRD ID: 10047055
Created: 2015-07-07
Species: All species
Last Modified: 2015-07-07
Status: ACTIVE



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