Clinical response to glatiramer acetate correlates with modulation of IFN-γ and IL-4 expression in multiple sclerosis

Abstract

Lymphoproliferation to GA did not differentiate GA-R from GA-HR/NR. However, reduced IFN-gamma expression and stable IL-4 expression in anti-CD3/CD28-stimulated PBMC, and an increased IL-4/IFN-gamma ratio was associated with favorable clinical response. More data are needed to validate the prospective use of IL-4/IFN-gamma expression in PBMC as a biomarker of clinical response to GA for individual patients.

Patterns of Th1/Th2 Cytokines Predict Clinical Response in Multiple Sclerosis Patients Treated with Glatiramer Acetate

“…This finding is in line with previous studies which demonstrated that clinical and immune responses correlated in patients treated with GA [12,13,15]. In a study on 36 RRMS patients treated with GA over 2 years, Valenzuela et al [12] observed an increased IL-4/IFN-γ ratio to be associated with a favorable clinical outcome. However, results of several studies were controversial, which is most likely due to short follow-up periods as one important factor [13,15].…”

“…Consequently, there is an ongoing search for biomarkers that could help to monitor efficiency of GA treatment in vivo [11]. Several studies suggest that the clinical response to GA in MS may correlate with the modulation of cytokines including interleukin (IL)-4 and interferon-γ (IFN-γ) [12,13,14,15]. …”

Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate

“…GA ameliorates MS and increases the period of remission in MS patients as well as reducing the EAE clinical scores in mice affected with this disease [1,3,4,7,8,9,16]. The major mechanism attributed to the effect of GA is shifting the immune system from an inflammatory Th1 to an anti-inflammatory Th2 type Research Article [1,4].…”

“…This drug is thought to mediate its beneficial effects by induction of GAspecific T helper (Th) 2 cells. IFN-g, a Th1 cytokine production is reduced and the ratio of IL-4/IFN-g significantly increased in MS patients treated with GA [4], suggesting a shift from Th1 to Th2 after therapy with GA. In addition, GA induces the activation of Treg cells [5] and inhibits the secretion of IL-12p70 after stimulating dendritic cells (DCs) with CD40L, resulting in increased IL-4 and decreased IFN-g release by T cells stimulated with GA-pretreated DCs [6].…”

Glatiramer Acetate Treatment of Multiple Sclerosis: An Immunological Perspective

“…Because myelin-reactive T cells appeared to be of a Th2 phenotype, this suggested GA could alter the pathogenic potential of myelin-reactive T cells and participate in bystander suppression. Importantly for the MS patients, the Th2 response observed correlated with the clinical benefit (22).…”