title: Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot.
abstract: OBJECTIVE
  Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed.
  
  
  METHODS
  The immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects.
  
  
  RESULTS
  When compared with diabetic control subjects and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of anti-inflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic control subjects and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot.
  
  
  CONCLUSIONS
  Together, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Uccioli
authors.forename: Anna
authors.initials: A
authors.lastname: Sinistro
authors.forename: Cristiana
authors.initials: C
authors.lastname: Almerighi
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaprini
authors.forename: Antonella
authors.initials: A
authors.lastname: Cavazza
authors.forename: Laura
authors.initials: L
authors.lastname: Giurato
authors.forename: Valeria
authors.initials: V
authors.lastname: Ruotolo
authors.forename: Francesca
authors.initials: F
authors.lastname: Spasaro
authors.forename: Erika
authors.initials: E
authors.lastname: Vainieri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rocchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergamini
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000097:blood; D017209:Apoptosis; D016207:Cytokines / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D005434:Flow Cytometry; D020233:Gait Disorders, Neurologic / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D009000:Monocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D012016:Reference Values
chemical_list: D015703:Antigens, CD; D016207:Cytokines