Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot

Luigi Uccioli, Anna Sinistro, Cristiana Almerighi, Chiara Ciaprini, Antonella Cavazza, Laura Giurato, Valeria Ruotolo, Francesca Spasaro, Erika Vainieri, Giovanni Rocchi, Alberto Bergamini

Research output: Contribution to journalArticlepeer-review

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. RESEARCH DESIGN AND 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.

Original languageEnglish
Pages (from-to)350-355
Number of pages6
JournalDiabetes Care
Volume33
Issue number2
DOIs
Publication statusPublished - Feb 2010

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

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