Cytokine profile in relapsing-remitting multiple sclerosis patients and the association between progression and activity of the disease

Multiple sclerosis (MS) is a progressive immune-mediated disease caused by demyelination of the central nervous system. Cytokines and their receptors have an important role in the evolution of MS lesions, and pro- and anti-inflammatory cytokine levels have been found to correlate with changes in MS disease activity. The aims of the present study were to evaluate the pro-inflammatory [tumor necrosis factor (TNF)-alpha and interleukin (IL) -1 beta, -6 and -12], T helper (Th) 1 [interferon (IFN)-gamma], Th17 (IL-17) and Th2 (IL-4 and -10) cytokine serum levels in relapsing-remitting (RR)-MS patients and to evaluate the association between the cytokine profile and the progression and activity of the disease. Serum cytokine levels were assessed using enzyme linked-immunosorbent assays in 169 RR-MS patients in the remission clinical phase and 132 healthy individuals who were age-, gender-, ethnicity- and body mass index-matched. Disability and activity of the disease were evaluated using the Expanded Disability Status Scale and magnetic resonance imaging with gadolinium, respectively. IFN-gamma and IL-6, -12 and -4 levels were higher in RR-MS patients compared to controls (P=0.0009, 0.0114, 0.0297 and 0.0004, respectively). IL-1 levels were higher in controls compared with RR-MS patients. IL-4 levels were higher in RR-MS patients with mild disability compared to those with moderate and severe disability (P=0.0375). TNF-alpha and IL-10 levels were higher in RR-MS patients with inactive disease compared with those with active disease. IL-17 levels showed a trend towards being higher in RR-MS patients with inactive disease compared to those with active disease (P=0.0631). Low TNF-alpha and high IFN-gamma levels were independently associated with RR-MS (P=0.0078 and 0.0056, respectively) and also with the activity of the disease (P=0.0348 and 0.0133, respectively). Results indicated that RR-MS patients, even in the remission clinical phase, exhibit a complex system of inflammatory and anti-inflammatory cytokines that may interact to modulate the progression and activity of the disease.