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Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study
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  1. R Furlana,
  2. M Filippib,
  3. A Bergamia,
  4. M A Roccab,
  5. V Martinellic,
  6. P L Poliania,
  7. L M E Grimaldid,
  8. G Desinae,
  9. G Comic,
  10. G Martinoa
  1. aExperimental Neuroimmunotherapy Unit, bNeuroimaging Research Unit, cClinical Trials Unit, dNeuroimmunology Unit, Department of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy, eDepartment of Neurology, Casa Sollievo della Sofferenza Scientific Institute, San Giovanni Rotondo (FG), Italy
  1. Dr Gianvito Martino, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Telephone 0039 02 26434867; fax 0039 02 26434855; emailg.martino{at}hsr.it

Abstract

The cysteine protease caspase-1 plays a crucial part in the inflammatory process due to its ability to proteolitically activate proinflammatory cytokine precursors, such as interleukin (IL)-1β and IL-18. Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS in which the pathogenic process is mainly orchestrated by proinflammatory cytokines.

 The role of caspase-1 in multiple sclerosis was evaluated by measuring its mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven patients with relapsing-remitting multiple sclerosis every 15 days over a 1 year period. The recorded levels were compared with clinical and MRI evidence of disease activity. Brain MRI was performed monthly in each patient.

 Caspase-1 mRNA levels were significantly increased in PBMCs from patients with multiple sclerosis compared with healthy controls (p<0.001). In patients with multiple sclerosis, a twofold to threefold increase of caspase-1 mRNA mean level was found in the week preceding an acute attack (p<0.05). The magnitude of caspase-1 mRNA increase correlated with the number of new (p=0.01) but not persisting gadolinium enhancing brain MRI lesions.

 In conclusion, caspase-1 might be involved in the immune mediated process underlying CNS inflammation and might represent a suitable peripheral immunological marker of disease activity in multiple sclerosis.

  • multiple sclerosis
  • caspase-1
  • proinflammatory cytokines
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