high energy demand. SEEC is based on removal of tissue during thecourse of arthritis, and subsequent determination of oxygen con-sumption. Small weighed pieces of the respective organ with a sizeof 4 mm are placed in 24-well multidishes with integrated oxygensensors, which allows for non-invasive detection of oxygen con-sumption in vitro. Results: In draining lymphoid nodes, we were ableto observe a marked increase in oxygen consumption during thecourse of arthritis. Sympathectomy prior to immunization increasesenergy consumption in draining lymph nodes, which is most proba-bly a sign of retention of leucocytes in the lymph node. Conclusions:The SEEC technique enables us to identify locations of high energydemand that are involved in the initiation and continuation of theautoimmune process in an animal model of arthritis.

http://dx.doi.org/10.1016/j.bbi.2012.07.078

55. Blockade of the neuropilin-2/plexin A2 receptor – A newtreatment of rheumatoid arthritis?J. Kunath, R. Straub

Laboratory of Experimental Rheumatology and Neuroendocrine Immu-nology, Department of Internal Medicine I, University Hospital ofRegensburg, Regensburg, Germany

Background: The loss of sympathetic nerve fibers (SNF) is a gen-eral principle in inflammatory diseases. Since sympathetic neuro-transmitters exert anti-inflammatory effects at increasedconcentrations, their loss in inflamed tissue is reasonable to over-come infection. However, this mechanism is unfavorable in chronicinflammation like rheumatoid arthritis (RA). Semaphorins are majorfactors involved in axon guidance and repulsion mediated by a neu-ropilin-2/ Plexin A2 receptor complex on nerve endings. We pro-posed that antagonizing semaphorin binding to its receptor cankeep nerve fibers in the inflamed area and may be a new therapeuticprinciple in treatment of RA. In this study, we wanted to test theneutralizing effects of polyclonal antibodies to plexin A2 on semaph-orin 3F-induced nerve fiber repulsion. Methods: A neurite outgrowthassay was used to investigate the behavior of nerve fibers from sym-pathetic trunk ganglia of postnatal mice. Results: Nerve repulsioncaused by semaphorin 3F is about 35–50%. Repulsion can be com-pletely abrogated by a polyclonal anti-plexin A2 antibody in a con-centration of 157 nmol/l (to 0–9%; p < 0.005). Similarly, anantibody against neuropilin-2 can also abrogate repellent factor –induced repulsion. Conclusion: This study provided us with a firstimportant tool to manipulate sympathetic nerve fiber repulsion.We are presently testing the antibodies in the animal model of col-lagen type II – induced arthritis.

http://dx.doi.org/10.1016/j.bbi.2012.07.079

56. Age dependant effects of the PPAR-gamma agonist rosiglit-azone on the brain and periphery during systemic LPS-inducedinflammation in ratsS. Koenig a, T. Wenz b, G.N. Luheshi c, R. Gerstberger a, J. Roth a,C. Rummel a

a Institute for Veterinary-Physiology and -Biochemistry, Justus-Liebig-University Giessen, Frankfurter Str. 100, Giessen 35392, Germanyb Institute for Genetics, University of Cologne, Cologne, Germanyc Douglas Mental Health University Institute, McGill University, Mon-treal, Quebec, Canada

Aging is associated with altered immune responses to stimuli suchas lipopolysaccharide (LPS) and a mitochondrial decline is proposedto be a main underlying factor in age-related diseases. Recently, ros-iglitazone (RZG), a peroxisome proliferator-activated receptor (PPAR)

gamma agonist was shown to exert anti-inflammatory properties andto induce a key regulator of mitochondrial biogenesis, namely, PPAR-gamma co-activator-1-alpha (PGC-1alpha). Here, we aimed to furtherelucidate age-dependent changes in signaling pathways and sicknessresponse during LPS-induced inflammation and to test potential ben-eficial effects of rosiglitazone. Pretreatment of old (24 months) andyoung (2 months) rats with RZG or solvent was followed by intraperi-toneal injection of LPS (100 lg/kg) or saline. 24 h after stimulationblood, brain and liver were withdrawn for further analysis. We foundage-dependent differences in fever and severity of other sicknesssymptoms after LPS-stimulation. Pretreatment with rosiglitazone,however, did not alter this response in young or old rats. Neverthe-less, analysis of the liver by RT-PCR revealed increased mRNA-levelsof markers of mitochondrial biogenesis in saline-injected and RZG-pretreated animals. Interestingly, several plasma cytokines includinginterleukin (IL)-6, IL-10, and IL-1ra and brain/liver inflammatorymediators such as nuclear factor IL-6 showed age-dependent changesindependent of RZG-injections. Overall, beneficial effects of RZGcould not be revealed in the current experimental paradigm. None-theless, our results reveal further insights into changes of brain andperipheral inflammatory mediators during aging and LPS-inducedinflammation.

http://dx.doi.org/10.1016/j.bbi.2012.07.080

57. Anxiety about relationships is linked to alterations in cortisolproduction and cellular immunityL.M. Jaremka a, R. Glaser a, T.J. Loving b, W.B. Malarkey a, J.R. Stowell c,J.K. Kiecolt-Glaser a

a The Ohio State University College of Medicine, Institute for BehavioralMedicine Research, 460 Medical Center Drive, Columbus, OH 43026,United Statesb The University of Texas at Austin, United Statesc Eastern Illinois University, United States

Although evidence suggests that attachment anxiety mayincrease risk for health problems, the mechanisms are not wellunderstood. Married couples (N = 85, Mage = 38.67) provided salivasamples over three days and blood samples on two occasions. Partic-ipants with higher attachment anxiety produced more cortisol andhad fewer numbers of CD45+ T cells, CD3+ T cells, CD3+CD4+ helperT cells, and CD3+CD8+ cytotoxic T cells than those with lower attach-ment anxiety. Higher cortisol was also related to fewer numbers ofCD45+, CD3+, CD3+CD4+, and CD3+CD8+, which is mechanisticallyconsistent with research showing that cortisol alters the cellularimmune response. These data suggest that attachment anxietymay have physiological costs and provide a glimpse into the path-ways through which social relationships impact health. The currentstudy also extends attachment theory in an important new directionby utilizing a psychoneuroimmunological approach to the study ofattachment anxiety, stress, and health.

http://dx.doi.org/10.1016/j.bbi.2012.07.081

58. Effects of regular exercise and weight loss on inflammatorybiomarkers in individuals with high blood pressureP.J. Mills, K. Wilson, J. Sadja, B. Woods, C. Pruitt, L. Redwine, G.Schmid-Schonbein, S. Hong

UCSD, Behavioral Medicine, La Jolla, CA 92103-0804, United States

Increased cardiorespiratory fitness and decreased weight areassociated with a reduced inflammatory state. This study prospec-tively examined contributions of cardiopulmonary fitness, BMI, andBP on circulating IL-6 and TNF-ain 34 pre-hypertensive (BP > 120/

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80 < 140/90 mmHg) and 37 hypertensive (BP >140/90 < 179/109 mmHg) sedentary men and women (20–60 years; BMI 23.5–36 kg/m2). Participants were randomized to a 3-month: exerciseintervention, exercise plus diet (DASH diet) intervention, or waitlistcontrol. Cardiorespiratory fitness (mL/kg/min) increased (F = 8.37;p < 0.001), BP decreased (F = 3.56; p = 0.03), and BMI marginallydecreased (F = 2.86; p = 0.064) in the exercise and exercise plus dietgroups but not in the waitlist group. Linear regressions predictingpost-intervention inflammatory markers included independent vari-ables: the respective pre-intervention inflammatory marker; age &gender; pre- and post-intervention BMI; pre- and post-interventioncardiorespiratory fitness; pre- and post-intervention BP; total min-utes spent on cardio and total minutes spent on weights. Post-inter-vention TNF-awas predicted by pre-intervention TNF-a(beta = 0.621; p < 0.001) and total cardio exercise minutes(beta = �0.235; p = 0.018) (final model R = 0.667; F = 20.6;p < 0.001). Post-intervention IL-6 was predicted by pre-interventionIL-6 (beta = .344; p = 0.004), pre- (beta = 1.34; p = 0.004) and post-(beta = �1.08; p = 0.018) intervention BMI and total exercise(beta = .328; p = 0.006) (final model R = 0.662; F = 8.9; p < 0.001).Findings indicate that the anti-inflammatory benefit of regular exer-cise is derived from the time spent regularly exercising (independentof actual improved cardiorespiratory fitness) and/or the existing aswell as change in body mass.

http://dx.doi.org/10.1016/j.bbi.2012.07.082

59. Long-term amphetamine treatment increases inflammatorylung reaction and reduces upper airway reactivity after allergiclung inflammation in ratsE.K. Hamasato a, A. Ligeiro de Oliveira b, A. Lino-dos-Santos-Franco c,B. Golegã Acceturi c, I. Daufenback Machado d, J.A. Gimenes Júnior c,R. de Paula Vieira b, S. Poliselli Farsky d, W. Tavares-de-Lima c,J. Palermo-Neto a

a Neuroimmnunomodulation Research Group, Department of Pathology,São Paulo, Brazilb Department of Biophotonics Applied to Health Sciences, Nove de JulhoUniversity, Brazilc Department of Pharmacology, University of São Paulo, Brazild Department of Clinical and Toxicological Analyses, Faculty of Pharma-ceutical Sciences, Brazil

The purpose of this study was to investigate the repercussions oflong-term AMPH treatment on the magnitude of allergic lunginflammation. Male Wistar rats were treated with AMPH or vehicle(PBS) during 21 days and sensitized with ovalbumin (OVA) one weekafter the first injection of vehicle or AMPH. Fourteen days after thesensitization, the rats were challenged with OVA by aerosol and,24 h later the parameters were analyzed. In rats treated with AMPH,the OVA challenge exacerbated the increased cell recruitment intothe lung and the cellular expression of ICAM-1, PECAM-1 and Mac-1 of cells recovered in bronchoalveolar lavage. Similarly, elevatedlevels of IL-4 but decreased levels of IL-10 were also found in sam-ples of lung explants from allergic rats after AMPH treatment. Con-versely, the ex-vivo tracheal reactivity to methacholine (MCh) wasreduced by AMPH treatment, whereas the force contraction of tra-cheal segments due to in vitro antigen challenge did not alter. Ourfindings suggest that lung inflammation and upper airway reactivitydue to OVA-challenge are under distinct control of AMPH long-termtreatment. Our data strongly indicate that AMPH modulates posi-tively the allergic lung inflammation by mechanisms involving theincrease of ICAM-1, PECAM-1, Mac-1 and IL-4 and abrogates therelease of anti-inflammatory cytokine IL-10.

http://dx.doi.org/10.1016/j.bbi.2012.07.083

60. Indoleamine 2,3-dioxygenase mediates anhedonia and anxi-ety-like behaviors caused by peripheral lipopolysaccharideimmune challengeJ.C. O’Connor, A. Salazar, B.L. Gonzalez-Rivera, L. Redus, J.M. Parrott

University of Texas Health Science Center at San Antonio, 7703 FloydCurl Dr., San Antonio, TX, United States

Upregulation of indoleamine 2,3-dioxygenase (IDO) by proin-flammatory cytokines has been implicated as a biological mediatorof inflammation-related mood disorders. Here, we sought to deter-mine whether peripheral immune challenge with Escherichia coli,lipopolysaccharides (LPS) precipitates the development of transla-tionally relevant depression-like behaviors and to investigate therole of IDO in mediating these LPS-induced behaviors. Intraperito-neal injection of C57BL/6J mice with LPS resulted in a robust, buttransient, reduction in exploratory locomotor activity (eLMA) thatreturned to near baseline levels by 24 h. Sucrose preference, a pre-clinical correlate of anhedonia, was diminished by more than 20%in LPS-treated compared to saline treated control mice, and LPSinduced a significant increase in anxiety-like behavior at 24 h thatwas independent eLMA. Pretreatment of mice with an IDO inhibi-tor, 1-methyltryptophan (1MT), ablated the anxiogenic effects ofLPS, while having no impact on sickness associated changes inbody weight or eLMA. Additionally, 1MT pretreatment attenuatedthe LPS-induced reduction in sucrose preference, which was alsoconfirmed in IDO-1 null mice. Interestingly, acute systemic admin-istration of L-kynurenine, the enzymatic product of IDO, precipi-tated an anhedonic and anxiogenic effect in naïve mice withouteffect on eLMA. In a preclinical model, these data implicate IDOas a pivotal mediator of LPS-induced depression- and anxiety-likebehavior.

http://dx.doi.org/10.1016/j.bbi.2012.07.084

61. Cultural differences in the link between supportive relation-ships and proinflammatory cytokinesJ. Chiang, N.I. Eisenberger, T.E. Seeman, S.E. Taylor

University of California, Los Angeles, Los Angeles, CA 90095, United States

Social relationships influence physical health, possibly by influ-encing systemic inflammation. We examined whether positive, neg-ative, and competitive daily social interactions predict levels ofproinflammatory cytokines IL-6 and the soluble receptor for tumornecrosis factor-a (sTNFaRII) and their reactivity to a social stressor.One hundred twenty-two healthy university students and employ-ees completed daily diaries that assessed positive, negative, andcompetitive social interactions for 8 days. Participants then engagedin laboratory-based social stress tasks, and IL-6 and sTNFaRII werecollected from oral mucosal transudate at baseline and at 25 and80 min post-stressor. Negative social interactions predicted elevatedsTNFaRII at baseline, and competitive social interactions predictedmarginally higher levels of IL-6 at baseline and significantly higherlevels of sTNFaRII at baseline. Negative social interactions were pre-dictive of IL-6 and sTNFaRII 25 min post-stressor. For competitiveinteractions, participants reported: (1) competitive leisure-timeactivities, (2) academic/work-related competitive events, and (3)competing for another person’s attention. Internal analyses revealedthat academic/work-related competitive events were significantlyassociated with baseline IL-6 and sTNFaRII, and competing foranother’s attention was predictive of baseline IL-6. Daily negativeand competitive social interactions are associated prospectivelywith heightened proinflammatory cytokine activity perhaps becausethey represent daily interpersonal stressors. Competing foranother’s attention and academic/work related competitive eventsmight be particularly related to proinflammatory activity, possibly

J. Chiang et al. / Brain, Behavior, and Immunity 26 (2012) S1–S50 S17