IL-6 may modulate the skeletal response to glucocorticoids during exacerbations of inflammatory bowel disease.
Whether inflammatory cytokines affect the skeletal response to glucocorticoid (GC) treatment is unclear. Our objectives were to (1) identify the cytokine(s) elevated during exacerbations of inflammatory bowel disease (IBD); (2) determine whether the cytokine(s) identified in this way is related to systemic GC sensitivity; and (3) examine whether cytokines and/or measures of GC sensitivity are related to changes in bone formation or resorption following GC therapy. We designed a combined cross-sectional and prospective study, including patients with active (n = 31) and inactive (n = 34) IBD as well as controls (n = 29). We assessed circulating concentrations of cytokines, PINP and betaCTX, as well as GC sensitivity in peripheral blood mononuclear cells. IL-6 was the only cytokine increased in active IBD, 2.35 (2.63) versus 1.64 (1.21) versus 1.31 (2.79) pg/microl active IBD, inactive IBD, and controls, respectively (median [interquartile range]) (P = 0.03, ANOVA). IL-6 was positively related to magnitude of GC sensitivity (beta = 0.02, 95% CI 0.008-0.04, P = 0.005). Following treatment with GC in active IBD, PINP decreased (P < 0.001), whereas betaCTX showed no significant change (P = 0.2). Subsequently, multiple regression analyses revealed that plasma IL-6 concentrations were inversely related to the extent of PINP suppression following GC (beta = 3.3, 95% CI 0.2-6.4, P = 0.04, adjusted for baseline PINP and duration of GC treatment), while no association was observed with GC sensitivity. In conclusion, IL-6 is elevated in active IBD and may protect against GC-induced suppression of bone formation via a mechanism which appears to be independent of systemic GC sensitivity.
Kriel
Muhammed
M
Clinical Science at South Bristol, University of Bristol, Bristol, UK. hashir.kriel@bristol.ac.uk
Sayers
Adrian
A
Fraser
William D
WD
Williams
Amanda M
AM
Koch
Alexander
A
Zacharowski
Kai
K
Probert
Chris S
CS
Tobias
Jonathan H
JH
D000328:Adult; D001851:Bone Diseases, Metabolic; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011239:Prednisolone / Q000009:adverse effects*; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction
D024042:Collagen Type I; D005938:Glucocorticoids; D015850:Interleukin-6; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D011239:Prednisolone