TNF-alpha and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica.
BACKGROUND
Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress.


METHODS
We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-alpha, IFN-gamma, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured.


RESULTS
We found almost undetectable levels of TNF-alpha, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-alpha and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector - regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship.


CONCLUSIONS
These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis.
Pentón-Rol
Giselle
G
Clinical Trials Division, Center for Biological Research, Havana, Cuba.
Cervantes-Llanos
Majel
M
Clinical Trials Division, Center for Biological Research, Havana, Cuba.
Martínez-Sánchez
Gregorio
G
Center for Research and Biological Evaluations, Institute of Pharmacy and Food Sciences, University of Havana, Havana, Cuba.
Cabrera-Gómez
José A
JA
International Center of Neurological Restoration, Havana, Cuba.
Valenzuela-Silva
Carmen M
CM
Clinical Trials Division, Center for Biological Research, Havana, Cuba.
Ramírez-Nuñez
Omar
O
Center for Research and Biological Evaluations, Institute of Pharmacy and Food Sciences, University of Havana, Havana, Cuba.
Casanova-Orta
Mayté
M
Center for Research and Biological Evaluations, Institute of Pharmacy and Food Sciences, University of Havana, Havana, Cuba.
Robinson-Agramonte
María A
MA
International Center of Neurological Restoration, Havana, Cuba.
Lopategui-Cabezas
Ileana
I
Higher Institute of Medical Sciences "Victoria de Girón", Havana, Cuba.
López-Saura
Pedro A
PA
Clinical Trials Division, Center for Biological Research, Havana, Cuba.