title: An adenosine A2A receptor agonist reduces interleukin-8 expression and glycosaminoglycan loss following septic arthrosis.
abstract: The purpose of this study was to determine whether an adenosine A(2A) receptor agonist (ATL146e) might augment the current treatment regimen of antibiotics plus irrigation and debridement to prevent the arthritic effects associated with joint sepsis. Staphylococcus aureus bacteria were injected into knees of rabbits, which were divided into 4 treatment groups (12 rabbits per group): no treatment, ATL146e only, antibiotics only, or antibiotics plus ATL146e. Analysis at days 1, 3, and 7 consisted of gross joint appearance, synovial fluid, serum, histologic, immunohistochemical, and biochemical analysis. Synovial fluid cultures at day 7 were negative in all antibiotic and antibiotic plus ATL146e treated knees indicating clearance of bacteria. Average WBC counts from synovial fluid aspirates significantly decreased with treatment of antibiotics alone and antibiotics plus ATL146e. Treatment with antibiotics plus ATL146e significantly decreased the Interleukin-8 content when compared to other treatment groups (p<0.001) indicating inflammatory response suppression. Histologic grading resulted in notably improved scores in the antibiotics plus ATL146e group compared to other treatment groups (p < or =0.001). Glycosaminoglycan assay values were significantly greater in the ATL146e plus antibiotics group compared to the untreated control group (p<0.04) indicating chondroprotection. The results of this study indicate that administration of an adenosine A(2A) agonist in combination with antibiotic therapy diminishes joint WBC chemotaxis and reduces joint inflammation, while not compromising the clearance of intraarticular bacteria in a rabbit model. Early bacterial clearance with modulation of the inflammatory response appears to prevent the early degradative effects of joint sepsis.
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia Health Center, Charlottesville, VA 22908, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Cohen
authors.forename: Brian M
authors.initials: BM
authors.lastname: Leo
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Baer
authors.forename: Maria A
authors.initials: MA
authors.lastname: Turner
authors.forename: Gina
authors.initials: G
authors.lastname: Beck
authors.forename: David R
authors.initials: DR
authors.lastname: Diduch
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis*; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000032:analysis*; D007958:Leukocyte Count; D011687:Purines / Q000627:therapeutic use*; D011817:Rabbits; D013583:Synovial Membrane / Q000473:pathology
chemical_list: C431129:ATL 146e; D058908:Adenosine A2 Receptor Agonists; D003509:Cyclohexanecarboxylic Acids; D006025:Glycosaminoglycans; D016209:Interleukin-8; D011687:Purines