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BLX‐1060: A dose‐dependent efficacy study in collagen‐induced arthritis in mice
Author(s) -
Sen Ananda Prasad,
Nag Abhijeet,
Vargas Hyang,
Dey Deben,
Neogi Partha,
Nag Bishwajit
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1127-a
Subject(s) - arthritis , medicine , sepsis , adjuvant , in vivo , immunization , tumor necrosis factor alpha , pharmacology , immunology , antibody , biology , microbiology and biotechnology
BLX‐1060 is a water‐soluble, amino acid conjugated small molecule with potent anti‐inflammatory properties. Here we present the studies undertaken on its oral in vivo efficacy in LPS‐induced sepsis and collagen‐induced arthritis (CIA) in mice. The LPS‐induced sepsis study was undertaken in male Swiss Webster mice (Simonsen), by administering with BLX‐1060, followed one hour later with LPS challenge. Terminal blood was collected after 1.5 Hours of LPS and serum analyzed for inflammatory cytokines. BLX‐1060 at 25, 50 and 100 mg/kg, PO, inhibited LPS induced TNF‐a (20–69%) production in a dose‐dependent manner. The CIA study was undertaken in male DBA/1LacJ mice (Jackson) by immunization with Bovine Type II collagen emulsified with Mycobacterium tuberculosis in Incomplete Freund's Adjuvant. The clinical symptoms of arthritic were observed from day 28 following immunization. BLX‐1060 at 25, 50 and 100 mg/kg/day, PO, significantly reduced clinical symptoms of arthritis, number of afflicted paws, and paw volume thickness. Histo‐pathological evaluation of the hind paws also showed significant changes in the 100 mg/kg vs the vehicle group. It is concluded that BLX‐1060 is a new orally acting TNF‐α inhibitor with potent anti‐arthritic properties.