Proinflammatory Modulation of the Surface and Cytokine Phenotype of Monocytes in Patients With Acute Charcot Foot
- Luigi Uccioli, MD1,
- Anna Sinistro, PHD2,
- Cristiana Almerighi, MD1,
- Chiara Ciaprini, MD1,
- Antonella Cavazza, PHD3,
- Laura Giurato, MD1,
- Valeria Ruotolo, MD1,
- Francesca Spasaro, MD1,
- Erika Vainieri, MD1,
- Giovanni Rocchi, MD2 and
- Alberto Bergamini, MD2
- 1Department of Internal Medicine, University of Rome “Tor Vergata,” Rome, Italy;
- 2Department of Public Health and Cellular Biology, University of Rome “Tor Vergata,” Rome, Italy;
- 3Department of Analytical Chemistry, University of Parma, Parma, Italy.
- Corresponding author: Alberto Bergamini, bergamini{at}med.uniroma2.it.
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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received June 24, 2009.
- Accepted October 16, 2009.
- © 2010 by the American Diabetes Association.
