Plasma tumour necrosis factor alpha (TNF-α) as a potential marker of multiple sclerosis – preliminary study

1 Klinika Neurologii i Udarów Mózgu, Uniwersytet Medyczny w Łodzi (decyzją Rektora Uniwersytetu Medycznego w Łodzi –
Uchwała nr 277/2014 z dn. 17.04.2014 roku – Klinika Neurologii i Epileptologii z Oddziałem Udarowym została przemianowana
na Klinikę Neurologii i Udarów Mózgu Uniwersytetu Medycznego w Łodzi)
2 Klinika Pediatrii, Onkologii, Hematologii i Diabetologii, Uniwersytet Medyczny w Łodzi
Adres do korespondencji: Klinika Neurologii i Udarów Mózgu, Uniwersytet Medyczny w Łodzi, ul. Żeromskiego 113, 90-549 Łódź,
* Praca finansowana przez Uniwersytet Medyczny w Łodzi z zadania badawczego nr 502-03/5-062-01/502-54-111 oraz funduszy własnych.
Artykuł został opracowany na podstawie rozprawy doktorskiej autorki pt.: Ocena ekspresji mikroRNA jako potencjalnych biomarkerów aktywacji układu immunologicznego w przebiegu stwardnienia rozsianego (SM) i zawiera znaczne jej fragmenty, wcześniej niepublikowane. Na przeprowadzenie badania uzyskano zgodę Komisji Bioetycznej Uniwersytetu Medycznego w Łodzi (Poprawka do Uchwały Komisji Bioetyki o projekcie eksperymentu medycznego nr RNN/234/12/KE z dnia 18.12.2012 r., poprawka nr KE/1827/13/P z dnia 15.10.2013 r., poprawka nr KB/447/14/P z dnia 15.04. 2014 r.), a także Dra n. med. Wiesława Chudzika, Dyrektora Uniwersyteckiego Szpitala Klinicznego im. Wojskowej Akademii Medycznej – Centralnego Szpitala Weteranów.

AKTUALN NEUROL 2014, 14 (2), p. 124–133
DOI: 10.15557/AN.2014.0014

Multiple sclerosis (MS) is a common chronic neurological disorder of the central nervous system that leads to progressive disability. The disease usually affects people between 20 and 40 years of age, with women being affected twice as often. Despite many years of research, very little is known about its pathogenesis. There are four distinct clinical presentations, of which the most common are the relapsing-remitting, the secondary progressive and primary progressive courses. The pathogenesis of MS is a complicated process, involving the disruption of the blood–brain and blood–cerebrospinal fluid barriers, secondary hyperplasia of the astroglia, inflammation, and neurodegeneration in a broad sense, among others. The inflammatory process involving various subpopulations of inflammatory cells plays a major role in the development of the disease, especially in its early stages. Previous studies have indicated that the tumour necrosis factor alpha (TNF-α), a proinflammatory cytokine, is particularly involved in the process. Aim of the study: To assess levels of TNF-α in the plasma of patients suffering from MS both undergoing a relapse and in remission, to correlate its concentration with clinical parameters, and to determine whether TNF-α could potentially serve as a marker of MS progression. The relationship between plasma concentrations of TNF-α and the number of leukocytes and subpopulations was analyzed in an attempt to identify major sources of TNF-α in the plasma in MS patients. Material and methods: Thirty-seven MS patients formed study groups (20 in the relapse group, 17 in the remission group). Thirty healthy volunteers formed the control group. Four millilitres of venous blood were collected from each participant. The blood was centrifuged (5000 rpm, 20 min, 23ºC) until the plasma layer could be separated and stored at –80ºC until the testing. TNF-α concentrations were determined using the ELISA method. Results and conclusions: The preliminary results did not show a statistically significant increase in TNF-α levels in the plasma of MS patients, both in the relapse and the remission groups. A positive correlation was found between the clinical severity of MS (measured by the EDSS score) and TNF-α levels in remission and relapse groups. However, it was not statistically significant. In a subgroup of patients in remission with low plasma levels of TNF-α (<1 pg/ml), higher TNF-α concentrations correlated with greater disability (EDSS score). WBC counts were statistically significantly higher in patients undergoing a relapse compared to the joint group of MS patients in relapse and in remission. Preliminary findings of small studies indicate that TNF-α plasma concentrations could potentially reflect the activity of underlying pathological processes in MS. Further studies on larger groups of patients are necessary to confirm the hypothesis as well as in order to correlate TNF-α concentrations in blood and the cerebrospinal fluid.

Keywords: multiple sclerosis (MS), central nervous system, inflammation, tumour necrosis factor alpha (TNF-α), ELISA, marker, plasma