title: Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells.
abstract: BACKGROUND
  CD8 lymphocytes play an important role in the pathogenesis of COPD. Corticosteroids and phosphodiesterase 4 (PDE4) inhibitors are anti-inflammatory drugs used for COPD treatment. Little is known of the combined effect of these drugs on COPD CD8 cells. We studied the effect of corticosteroid combined with PDE4 inhibitors on cytokine release form circulating and pulmonary CD8 cells, and on glucocorticoid (GR) nuclear translocation.
  
  
  METHODS
  The effect of dexamethasone alone and in combination with the PDE4 inhibitors roflumilast and GSK256066 on cytokine release from circulating and pulmonary CD8 cells was measured. The effect of the compounds on nuclear translocation of GR and cyclic AMP-responsive element-binding protein (CREB) was studied using immunofluorescence.
  
  
  RESULTS
  Dexamethasone inhibited cytokine release from COPD CD8 cells in a concentration dependent manner. PDE4 inhibitors enhanced this anti-inflammatory effect in an additive manner. PDE4 inhibitors did not increase corticosteroid induced GR nuclear translocation. PDE4 inhibitors, but not corticosteroid, increased phospho-CREB nuclear translocation.
  
  
  CONCLUSIONS
  The combination of corticosteroids and PDE4 inhibitors results in an additive anti-inflammatory effect in COPD CD8 cells. This enhanced anti-inflammatory effect could translate to important clinical benefits for patients with COPD.
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust Southmoor Road, Manchester, M23 9LT, UK. seamus.grundy@aintree.nhs.uk.
authors.forename: Seamus
authors.initials: S
authors.lastname: Grundy
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust Southmoor Road, Manchester, M23 9LT, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Plumb
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust Southmoor Road, Manchester, M23 9LT, UK.
authors.forename: Manminder
authors.initials: M
authors.lastname: Kaur
authors.affiliation: School of Medicine and Manchester Academic Health Science Centre, University of Manchester, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Ray
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust Southmoor Road, Manchester, M23 9LT, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000276:immunology; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D005938:Glucocorticoids / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D058988:Phosphodiesterase 4 Inhibitors
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