Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study

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)-1 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. (J Neurol Neurosurg Psychiatry 1999;67:785-788)

Inflammasome signaling at the heart of central nervous system pathology

“…On the other hand, caspase activation has been identified as the key perpetrator of cell death in a variety of neurologic diseases. For instance, in experimental autoimmune encephalomyelitis (EAE), a model of MS, caspase-1-deficient mice showed a reduced pathology of MS (Furlan et al, 1999). In human cohort studies, notable upregulation of caspase-1 transcription in peripheral blood mononucleocytes in MS patients was observed as compared to healthy control subjects (Huang et al, 2004).…”

Gene Expression Profile of Herpesvirus-Infected T Cells Obtained Using Immunomicroarrays: Induction of Proinflammatory Mechanisms

“…As HHV-6 is currently under investigation as a possible etiologic agent in MS (13), it is of interest that IL-18 is expressed in demyelinating lesions of MS brains (7) and that levels of caspase 1, the regulatory enzyme of pro-IL-18, are elevated in the peripheral blood of MS patients (18,19). These studies suggest that activation of the IL-18 pathway may be involved in the development of this demyelinating disease.…”

Interleukin-18

“…Furthermore, the brains taken from patients with demyelinating MS exhibit up-regulation of IL-18 and IFN-␥ mRNA with the accompanying accumulation of Th1-specific T cells [164]. Finally, caspase-1-deficient mice exhibit decreased disease severity, and cells taken from MS patients have elevated caspase-1 levels [165,166].…”