Type II Activation of Monocytes in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an incurable autoimmune disease of the CNS. Although its cause is not known, immune cells are involved in the disease progression. Among these cells, type I monocytes are first to arrive to the brain and initiate inflammation; however, if monocytes are type II activated, they can inhibit inflammation. Previous research has shown that immune responses can be modulated by treatments, such as glatiramer acetate (GA) and immune complexes (IC). Therefore, we aimed to determine whether GA and IC can induce type II activation of monocytes in MS. Human blood monocytes from healthy volunteers and MS patients were stimulated in vitro with bacterial lipopolysaccharide (classical activation) in the presence or absence of GA and immune complexes (IC) composed of IVIG and human red blood cells (type II activation). Flow cytometry, ELISA and cytometric bead array were used to assess levels of marker expression and cytokine production in order to define the activation of monocytes. Interestingly, while both GA and IC induced type II activation of monocytes, the characteristics of these type II monocytes were distinct. We have found that monocytes from both healthy people and MS patients have significantly lower levels of inflammatory marker CD40 and higher levels of the anti-inflammatory cytokine IL-10 after treatment with IC. In contrast, GA treatment reduced the levels of CD40, CD86 and the inflammatory cytokine IL- 12. Moreover, the combined addition of GA and IC appeared to be more effective in type II activating monocytes than either agent alone. We also found that both CD14++CD16- and CD14+CD16+ monocyte subsets can be type II activated by the treatments; however, an interaction between the subsets impaired their response to the treatments. Our study suggests that treatments with GA and IC, especially in combination, are effective in type II activation of human monocytes and can be beneficial therapeutic approaches for multiple sclerosis.