title: Cholinergic anti-inflammatory pathway activity and High Mobility Group Box-1 (HMGB1) serum levels in patients with rheumatoid arthritis.
abstract: High Mobility Group Box-1 (HMGB1) is a cytokine implicated in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. The cholinergic anti-inflammatory pathway, a vagus nerve-dependent mechanism, inhibits HMGB1 release in experimental disease models. Here, we examine the relationship between vagus nerve activity and HMGB1 in patients with RA. We compared RR interval variability, an index of cardiac vagal modulation, HMGB1 and hsCRP serum levels, and disease activity scores in thirteen RA patients and eleven age- and sex-matched controls. In RA patients, serum levels of HMGB1 and hsCRP were elevated as compared with controls (HMGB1=71 ng/mL [45-99] vs. 18 ng/mL [0-40], P<0.0001; hsCRP=14.5 mg/L [0.7-59] vs. 1 mg/L [0.4-2.9], P<0.001). RR interval variability in RA patients was significantly decreased as compared with controls (HF=38 msec2 [14-80] vs. 288 msec2 [38-364], P<0.0001; rMSSD=20.9+/-9.79 msec, 52.6+/-35.3 msec, P<0.01). HMGB1 levels and RR interval variability were significantly related (rho=-0.49, P<0.01). HMGB1 serum levels significantly correlated with disease activity scores (DAS-28) in patients with RA (P=0.004). The study design does not enable a determination of causality, but the results are consistent with the hypothesis that decreased cholinergic anti-inflammatory pathway activity is associated with increased HMGB1 levels in patients with RA.
authors.affiliation: The Feinstein Institute for Medical Research, and Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY 11030, USA. rgoldst2@nshs.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Goldstein
authors.forename: Annette
authors.initials: A
authors.lastname: Bruchfeld
authors.forename: Lihong
authors.initials: L
authors.lastname: Yang
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Margot
authors.initials: M
authors.lastname: Gallowitsch-Puerta
authors.forename: Nirav B
authors.initials: NB
authors.lastname: Patel
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Huston
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Chavan
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rosas-Ballina
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Czura
authors.forename: Richard P
authors.initials: RP
authors.lastname: Sloan
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sama
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000378:metabolism* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D018678:Cholinergic Agents / Q000378:metabolism*; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D018678:Cholinergic Agents; D024243:HMGB1 Protein; D002097:C-Reactive Protein