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Increased interleukin 33 in patients with neuro-Behcet's disease: correlation with MCP-1 and IP-10 chemokines

Cellular & Molecular Immunology volume 11, pages 613–616 (2014)Cite this article

Neurological involvement in Behçet's disease (BD), namely, neuro-Behçet's disease (NBD), causes devastating central nervous system (CNS) complications and is present in 5% to 30% of patients with BD.1 Immunological and molecular pathways are involved in NBD and include the release of interleukin (IL)-1, -6 and -8, and TNF-α and IFN-γ into cerebrospinal fluid (CSF),2 which reflects a nonspecific inflammatory pattern that is compatible with auto-inflammatory disease pathways. IL-33 is an unconventional member of the IL-1 family that has been recently implicated in several inflammatory and autoimmune diseases.3 We document here, for the first time, that IL-33 is upregulated in the CNS of patients with NBD. We studied the IL-33 level and IL-33 mRNA expression in CSF and their correlation with the levels of the IP-10 and MCP-1 chemokines in 20 NBD patients, compared with those of 12 age-matched, non-inflammatory neurological disease (NIND) patients and 10 patients with headache attributed to Behçet's disease (HaBD). IL-33 was elevated in the CSF from NBD patients compared with those of disease controls. At the mRNA level, IL-33 was highly expressed in NBD. In parallel, nuclear factor κB (NF-κB), which mediates IL-33 transcription, was also elevated when compared with disease controls. Chemokine mRNA (IP-10 and MCP-1) was highly expressed in NBD compared with the disease controls. In summary, IL-33 levels are elevated in the central nervous system of patients with NBD, implicating IL-33 in BD neurological lesions.

BD is a complex, multisystem inflammatory disorder of unknown etiology. This disease typically manifests as recurrent oral and genital ulcerations and uveitis that are variably accompanied by symptoms affecting the skin, large vessels, gastrointestinal system and CNS. The precise mechanisms of tissue destruction in BD have not been fully elucidated. A number of viruses, including hepatitis viruses, parvovirus B19 and herpes simplex virus, has been implicated in the etiology of BD. All studied patients fulfilled the diagnostic criteria of the International Study Group for BD.4 Of the 22 NBD patients, 10 had parenchymal involvement (subacute neurological syndrome; brainstem involvement; hemispheric involvement with spinal cord involvement; bilateral pyramidal signs) and 12 patients had cerebral vein and arterial thrombosis.5 The treatment modalities consisted of immunosuppressive agents in combination with high oral doses or intravenous pulses of glucocorticosteroids.

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Acknowledgements

This work was supported by grants from the Ministry of Research and the Ministry of Health of Tunisia (Unit Research 12SP15 ‘Molecular expression of cellular interactions and modes of communication’).

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  1. Dr K Hamzaoui, Medicine Faculty of Tunis, El Manar Tunis University, 15 Rue DjebelLakdar 1007, Tunis, Tunisia. E-mail: kamel.hamzaoui@gmail.com

Authors and Affiliations

  1. Department of Basic Sciences, El Manar Tunis University, Faculty of Medicine of Tunis, Tunis, Tunisia

    Kamel Hamzaoui, Wajih Kaabachi & Agnes Hamzaoui

  2. Health Policy Research Center and Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran

    Afshin Borhani-Haghighi & Agnes Hamzaoui

  3. Department of Pneumology, Ministry of Health & Faculty of Medicine of Tunis, Tunis, Tunisia

    Agnes Hamzaoui

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  1. Kamel Hamzaoui
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  4. Agnes Hamzaoui
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Hamzaoui, K., Borhani-Haghighi, A., Kaabachi, W. et al. Increased interleukin 33 in patients with neuro-Behcet's disease: correlation with MCP-1 and IP-10 chemokines. Cell Mol Immunol 11, 613–616 (2014). https://doi.org/10.1038/cmi.2014.31

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