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Published on: April 11, 2012
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Inhibiting the inflammatory response in joint sepsis
Christopher J. Hogan1, Guo-Dong Fang, W. Michael Scheld
1Departments of Orthopaedic Surgery (C.J.H., D.R.D.) and Infectious Diseases (G-D.F., W.M.S., J.L.), The University of Virginia School of Medicine, Charlottesville, Virginia, U.S.A.
Summary
This study shows that WRC-0470 and rolipram significantly reduce white blood cell recruitment in a rabbit septic arthritis model. These findings suggest potential new treatments for infectious arthritis by targeting inflammation.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Background:
- Septic arthritis causes significant long-term joint damage.
- Inflammatory responses, driven by white blood cells, exacerbate bacterial-induced joint injury.
- Current interventions lack efficacy in reducing the inflammatory cascade of infectious arthritis.
Purpose of the Study:
- To evaluate the efficacy of WRC-0470, an adenosine analogue, and rolipram, a phosphodiesterase inhibitor, in reducing intra-articular white blood cell recruitment.
- To establish a rabbit model of infectious arthritis for therapeutic testing.
Main Methods:
- A rabbit model of infectious arthritis was induced using Escherichia coli lipopolysaccharide (LPS).
- Rabbits received intravenous WRC-0470, rolipram, or a combination therapy.
- Synovial fluid white blood cell counts were analyzed to assess treatment effects.
Main Results:
- A reproducible septic arthritis model was established using 200 ng of LPS.
- WRC-0470 (10 µg/kg/min) reduced white blood cell counts to 800 cells/mL (P <.01).
- Rolipram (10 µg/kg/min) reduced counts to 1,225 cells/mL (P <.05).
- Combination therapy showed synergistic effects, reducing counts to 1,090 cells/mL at 1.0 µg/kg/min (P <.01).
Conclusions:
- WRC-0470 and rolipram effectively decrease intra-articular white blood cell infiltration in a septic arthritis model.
- These agents demonstrate potential for limiting joint destruction in infectious arthritis.
- Further research is warranted to determine the clinical utility of these drugs.
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