RESEARCH - Is taurolidine (TRD) a candidate for treatment of RA?

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Clin Exp Rheumatol. 2007 Mar-Apr;25(2):211-8.

Is Taurolidine a candidate for treatment of rheumatoid arthritis?

Marcinkiewicz J, G³uszko P, Kontny E, Kwa¶ny-Krochin B, Bobek M,

Wierzchowski W, Ciszek M, Ma¶liñski W.

Department of Immunology, Jagiellonian University Medical College,

Cracow, Poland.

OBJECTIVE: To study the therapeutic potential of taurolidine (TRD), a

derivative of taurine with known anti-inflammatory and

anti-proliferative properties, in various experimental models of

synovitis.

METHODS: In vitro: fibroblast-like synoviocytes (RA FLS) isolated from

the synovial tissue of patients with rheumatoid arthritis (RA) were

cultured in the presence of either TRD or polyvinylpyrrolidine (PVP),

the pharmaceutical stabilizer of TRD, which was used as a control.

Proliferation of RA FLS and cytokine (IL-6 and IL-8) release were

measured. In vivo: (A). The effect of systemic TRD treatment on the

development of collagen-induced arthritis (CIA) in female DBA1/J mice

was investigated. Mice were treated either with intraperitoneal

injections of 1 ml of 2% Taurolin Boehringer Ingelheim (TRD +PVP) or

with PVP as placebo. The incidence of arthritis, myeloperoxidase (MPO)

activity in periarticular tissue, as well as serum concentration of

IgG specific to collagen II (IgG alphaCII) were determined. (. The

effect of intra-articular TRD treatment was studied in rabbits with

antigen-induced monoarthritis (AIA). After the induction of AIA of

right knees rabbits were treated either with intra-articular

injections of 0.5 ml of 2% Taurolin or 0.5ml PVP ( placebo). The

animals were examined for clinical signs of arthritis and diameter of

joints was measured. After termination of the experiment, the

arthritic knees were examined and histopathology of the joints was

assessed. In addition, serum amyloid A (SAA) concentration was

measured.

RESULTS: n vitro: TRD exerted cytotoxic effect on RA FLS when applied

at concentrations >100 microM. TRD at non-cytotoxic concentrations,

inhibited PDGF-triggered RA FLS proliferation, reduced IL-1beta -

stimulated production of IL-6 and slightly decreased intracellular

content of IL-8. In vivo: (A). Intraperitoneal treatment with Taurolin

significantly reduced the incidence (30%) of CIA when compared to the

control mice (79%). However, Taurolin failed to control the

development of CIA in mice with high serum level of IgG alphaCII

(>1000 U).(. Intra-articular application of 2% Taurolin resulted in

amelioration of AIA in all treated rabbits (reduced diameter of

arthritic joints and smaller rise of SAA level as compared to the

control animals). Histopathologic evaluation revealed pannus formation

in both groups and extensive necrotic lesions of synovial tissue

treated with TRD, suggesting synoviorthesis-like effect.

CONCLUSION: Results from AIA and from in vitro RA FLS studies suggest

that intra-articular administration of TRD could be used as a

" pharmacological scalpel " to remove the inflamed synovium. Our data

confirmed anti-inflammatory and anti-proliferative properties of TRD

in all experimental models encouraging further studies which should

evaluate its therapeutic potential in RA.

PMID: 17543144

http://www.ncbi.nlm.nih.gov/pubmed/17543144

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