Brief Communication

Increased Level of Caspase-1 in the Serum of Relapsing-remitting Multiple Sclerosis (RRMS) Patients


Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, in which proinflammatory cytokines play a critical role in the pathogenic formation of lesions. Caspase-1 is a cysteine protease that proteolytically cleaves precursors of interleukin (IL)-18 and IL-1β and turns them into their active forms. These inflammatory cytokines play an important role in the development of MS. The aim of the present study was the investigation of caspase-1 and its downstream products, IL-18 and IL-1β, in relapsing-remitting MS (RRMS) patients.
In this study, we used an ELISA assay to measure serum and cellular caspase-1 and serum levels of IL-18 and IL-1β in RRMS patients in the relapse phase (n=23) and healthy age-and gender-matched controls (n=19).
We observed that the caspase-1 level was significantly increased in the serum of MS patients compared to the healthy controls (p=0.03). Although caspase-1 concentration in the lysate of peripheral blood mononuclear cells (PBMCs) was higher than serum among patients and controls (p<0.001), no significant difference was found in cellular levels of caspase-1 between the two groups. There was no significant difference in serum levels of
IL-18 and IL-1β between patients and controls.
In this study, we found an elevation of extracellular caspase-1, as a reflection of its intracellular level, in the serum of RRMS patients during the relapse phase. Therefore, it suggests being a suitable peripheral biomarker of disease activity in multiple sclerosis.

1. Azami M, YektaKooshali MH, Shohani M, Khorshidi A, Mahmudi L. Epidemiology of multiple sclerosis in Iran: A systematic review and meta-analysis. PLoS One. 2019;14(4):e0214738.
2. Mills KH, Dungan LS, Jones SA, Harris J. The role of inflammasome-derived IL-1 in driving IL-17 responses.J. Leukoc. Biol. 2013;93(4):489-97.
3. Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, et al. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci Res. 2010;30(47):15811-20.
4. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009;31(2):331-41.
5. Millward JM, Løbner M, Wheeler RD, Owens T. Inflammation in the Central Nervous System and Th17 Responses Are Inhibited by IFN-γ–Induced IL-18 Binding Protein. J Immunol. 2010;185(4):2458-66.
6. Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, et al. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol. 2010;185(2):974-81.
7. Kallaur AP, Oliveira SR, Delicato de Almeida ER, Kaminami Morimoto H, Lopes J, de Carvalho Jennings Pereira WL, et al. Cytokine profile in relapsing‑remitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep. 2013;7(3):1010-20.
8. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-7.
9. Shaw PJ, Lukens JR, Burns S, Chi H, McGargill MA, Kanneganti T-D. Cutting Edge: Critical Role for PYCARD/ASC in the Development of Experimental Autoimmune Encephalomyelitis. J Immunol. 2010;184(9):4610-4.
10. Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming MA, et al. Activation of interferon-γ inducing factor mediated by interleukin-1β converting enzyme. Science. 1997;275(5297):206-9.
11. Imani D, Azimi A, Salehi Z, Rezaei N, Emamnejad R, Sadr M, et al. Association of nod-like receptor protein-3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing–remitting multiple sclerosis. Int. J Immunogenet. 2018;45(6):329-36.
12. Kadowaki A, Quintana FJ. The NLRP3 inflammasome in progressive multiple sclerosis. Brain. 2020;143(5):1286-8.
13. Franciotta D, Martino G, Zardini E, Furlan R, Bergamaschi R, Gironi M, et al. Caspase-1 levels in biological fluids from patients with multiple sclerosis and from patients with other neurological and non-neurological diseases. Eur Cytokine Netw. 2002;13(1):99-103.
14. Peelen E, Damoiseaux J, Muris A-H, Knippenberg S, Smolders J, Hupperts R, et al. Increased inflammasome related gene expression profile in PBMC may facilitate T helper 17 cell induction in multiple sclerosis. Mol Immunol. 2015;63(2):521-9.
15. Miao EA, Leaf IA, Treuting PM, Mao DP, Dors M, Sarkar A, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol. 2010;11(12):1136-42.
IssueVol 19 No 5 (2020) QRcode
SectionBrief Communication
Caspase 1 Inflammasomes Interleukin-1 beta Interleukin-18 Multiple sclerosis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Beheshti M, Salehi Z, Abolfazli R, Shirzad H, Izad M. Increased Level of Caspase-1 in the Serum of Relapsing-remitting Multiple Sclerosis (RRMS) Patients. Iran J Allergy Asthma Immunol. 19(5):534-538.