Inhibiting the inflammatory response in joint sepsis

Purpose: We created a rabbit model of infectious arthritis to test the effects of WRC-0470 (2-cyclohexylmethylidenehydarazinoadenosine), an adenosine analogue, and rolipram, a type IV phosphodiesterase inhibitor, on intra-articular white blood cell recruitment. Type of Study: Randomized trial involving mature rabbits. Methods: Intra-articular injections ranging from 0 to 2,000 ng of Escherichia coli lipopolysaccharide (LPS) were tested as the infectious stimulus. The optimal LPS amount was determined based on synovial fluid analysis for white blood cell counts. A separate cohort of rabbits then received various intravenous concentrations of either rolipram, WRC-0470, or a combination of the 2 medications. Synovial fluid aspirations after a 6-hour incubation were analyzed for white blood cell counts. Results: Intra-articular injections of 200 ng of LPS reproducibly generated an inflammatory response of 4,000 cells/mL of synovial fluid, establishing the use of this dose of LPS for our septic arthritis model. Following infusions of 10 μg/kg/min, the average white blood cell count dropped to 800 cells/mL for WRC-0470 (P