Immunopharmacology and Inflammation Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats Petra Hartmann a , Andrea Szabó a, ⁎, Gábor Erős a , Dóra Gurabi a , Gyöngyi Horváth b , István Németh c , Miklós Ghyczy d , Mihály Boros a a Institute of Surgical Research, University of Szeged, H-6720 Szeged, Pécsi u. 6, Hungary b Department of Physiology, University of Szeged, Szeged, Hungary c Department of Pathology, University of Szeged, Szeged, Hungary d Cologne, Germany abstract article info Article history: Received 6 May 2009 Received in revised form 27 August 2009 Accepted 8 September 2009 Available online 18 September 2009 Keywords: Carrageenan Synovium Diclofenac ICAM-1 Microcirculation intravital videomicroscopy We investigated the effects of exogenous phosphatidylcholine (PC) and non-steroidal diclofenac supplementation on polymorphonuclear cell influx in carrageenan-induced arthritis in rats. The microcirculatory consequences were evaluated by a novel method developed for direct intravital microscopic observation of the synovial membrane. Arthritis was induced by injection of a mixture of 2% λ-carrageenan and 4% kaolin into the knee joints and the animals were treated orally with PC (150 mg/kg twice daily), sodium diclofenac (0.5 mg/kg twice daily) or saline vehicle. Intravital videomicroscopy was used to investigate the leukocyte–endothelial interactions directly in the synovial membrane at 6 h after the challenge. The inflammation–induced thermal and mechanical secondary hyperalgesic reactions were assessed at 24 h, and the knee volume changes at 48 h after the insult. The development of arthritis was accompanied by a significant increase in the number of adherent leukocytes in the synovial postcapillary venules, but this increase was reduced significantly (by ∼ 40%) by PC, and slightly (by 22%) by diclofenac treatment. The perivascular infiltration of the neutrophil leukocytes and the intercellular adhesion molecule- 1 (ICAM-1) expressions were reduced only by PC treatment. The significant decrease (45%) in the thermal nociceptive latency, the 3-fold increase in the mechanical touch sensitivity and the knee cross-sectional area (which was increased by 35% by the arthritis induction) were significantly ameliorated by both treatments. The present study demonstrated the anti-inflammatory effects of PC in experimental arthritis. The therapeutic potential may be linked to the reduction of neutrophil leukocyte-mediated microcirculatory inflammatory reactions. © 2009 Elsevier B.V. All rights reserved. 1. Introduction The arthritis syndrome embraces various joint disorders with distinct etiologies, ranging from osteoarthritis to rheumatoid arthritis and gout (Helmick et al., 2008). Despite the increasing incidence, the therapeutic possibilities are still mostly limited to pain relief and inflammation reduction. Polymorphonuclear leukocytes are generally considered appropriate markers of inflammatory synovial reactions (Gál et al., 2005), however, they may also occur in a non-infectious process, such as in rheumatoid arthritis (Bennett and Skosey, 1977) and the spondylarthritides (Baeten et al., 2005). Indeed, certain recent findings reinforced the view that therapeutic approaches should be targeted more broadly and directly to the inhibition of polymorphonu- clear leukocyte trafficking (Hallett and Williams, 2008). The anti- inflammatory agents most commonly used for this purpose are non- steroidal anti-inflammatory drugs (NSAIDs). However, in around 15% of the patients, NSAID administration is accompanied by undesirable side- effects, including minor (abdominal pain and vomiting) or more serious (ulcers and bleeding) gastrointestinal and hematological complications (Furst, 1994; Singh et al., 1996). Phosphatidylcholine (PC) is a ubiquitous membrane component, but a number of recent studies have demonstrated an anti-inflammatory potential for PC and its metabolites in various conditions linked to leukocyte activation, such as ischemia (Duan and Karmazyn, 1990), irradiation (Soloviev et al., 2002), oxidative stress (Aleynik and Lieber, 2003), and endotoxin or bile-induced injuries (Dial et al., 2008; Eros et al., 2006). Examinations involving intravital microscopy have clearly revealed that the neutrophil leukocytes are the first major cell population European Journal of Pharmacology 622 (2009) 58–64 ⁎ Corresponding author. Tel.: +36 62 545103; fax: +36 62 545743. E-mail addresses: petra@expsur.szote.u-szeged.hu (P. Hartmann), sza@expsur.szote.u-szeged.hu (A. Szabó), eg@expsur.szote.u-szeged.hu (G. Erős), doridzsi@gmail.com (D. Gurabi), horvath@phys.szote.u-szeged.hu (G. Horváth), estvannemeth@yahoo.com (I. Németh), miklos.ghyczy@netcologne.de (M. Ghyczy), boros@expsur.szote.u-szeged.hu (M. Boros). 0014-2999/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2009.09.012 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar