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Volume 25
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10.3390/molecules25010020
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Article

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

by
Eugenio Cavalli
1,
Emanuela Mazzon
1,
Maria Sofia Basile
2,
Santa Mammana
1,
Manuela Pennisi
2,
Paolo Fagone
2,
Reni Kalfin
3,
Vanja Martinovic
4,
Jovana Ivanovic
4,
Marko Andabaka
4,
Sarlota Mesaros
4,
Tatjana Pekmezovic
4,
Jelena Drulovic
4,
Ferdinando Nicoletti
2,* and
Maria Cristina Petralia
1
1
IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
2
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
3
Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Block 23 1113 Sofia, Bulgaria
4
Clinic of Neurology, Clinical Center of Serbia, Dr Subotica 6, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Molecules 2020, 25(1), 20; https://doi.org/10.3390/molecules25010020
Received: 8 November 2019 / Revised: 12 December 2019 / Accepted: 17 December 2019 / Published: 19 December 2019
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Abstract

We evaluated the in silico expression and circulating levels of interleukin (IL)37 in patients with different forms of multiple sclerosis (MS) and also upon treatment with different disease-modifying drugs. The combined interpretation of the resulting data strengthens and extends the current emerging concept that endogenous IL37 plays an important role in determining onset and progression of MS. The in silico analysis revealed that production of IL37 from cluster of differentiation (CD)4+ T cells from MS patients was reduced in vitro as compared to healthy controls. The analysis of the datasets also demonstrated that “higher” levels of IL37 production from PBMC entailed significant protection from MS relapses. In addition, the in vivo part of the study showed that IL37 was selectively augmented in the sera of MS patients during a relapse and that treatment with the high potency disease-modifying drug fingolimod significantly increased the frequency of patients with circulating blood levels of IL37 (6/9, 66%) as compared to patients receiving no treatment (n = 48) or platform therapy (n = 59) who had levels of IL37 below the limit of the sensitivity of the assay. This finding therefore anticipates that fingolimod may at least partially exert its beneficial effects in MS by upregulating the production of IL37. View Full-Text
Keywords: cytokines; interleukin 37; multiple sclerosis; fingolimod cytokines; interleukin 37; multiple sclerosis; fingolimod
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MDPI and ACS Style

Cavalli, E.; Mazzon, E.; Basile, M.S.; Mammana, S.; Pennisi, M.; Fagone, P.; Kalfin, R.; Martinovic, V.; Ivanovic, J.; Andabaka, M.; Mesaros, S.; Pekmezovic, T.; Drulovic, J.; Nicoletti, F.; Petralia, M.C. In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod. Molecules 2020, 25, 20. https://doi.org/10.3390/molecules25010020

AMA Style

Cavalli E, Mazzon E, Basile MS, Mammana S, Pennisi M, Fagone P, Kalfin R, Martinovic V, Ivanovic J, Andabaka M, Mesaros S, Pekmezovic T, Drulovic J, Nicoletti F, Petralia MC. In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod. Molecules. 2020; 25(1):20. https://doi.org/10.3390/molecules25010020

Chicago/Turabian Style

Cavalli, Eugenio, Emanuela Mazzon, Maria S. Basile, Santa Mammana, Manuela Pennisi, Paolo Fagone, Reni Kalfin, Vanja Martinovic, Jovana Ivanovic, Marko Andabaka, Sarlota Mesaros, Tatjana Pekmezovic, Jelena Drulovic, Ferdinando Nicoletti, and Maria C. Petralia. 2020. "In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod" Molecules 25, no. 1: 20. https://doi.org/10.3390/molecules25010020

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