Increased T‐lymphocyte interleukin‐6 binding in patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) represents a T-cell-mediated autoimmune demyelinating disease of the central nervous system associated with altered immunoregulation. Interleukin (IL)-6 is a cytokine that has several effects on the neuroimmune system. Specific IL-6 receptors have been found in human lymphocytes and neuroglial cells. The aim of the present study was to assay IL-6 binding on peripheral blood T lymphocytes in MS patients. We found that T cells from MS patients had significantly more IL-6 receptors [Bmax: 279 +/- 7 vs. 246 +/- 8 (mean +/- SEM) receptors/cell, in patients and controls, respectively], whereas Kd values were similar to those of healthy subjects [26.8 +/- 0.7 vs. 25.4 +/- 0.6 (mean +/- SEM) pM, in patients and controls, respectively]. Significant (P < 0.05) differences in IL-6 binding values were observed between stable patients and those relapsing (272 +/- 9 vs. 300 +/- 12 (mean +/- SEM) receptors/cell, respectively). We found significantly (P < 0. 001) higher amounts of IL-6 receptors on CD4+ T cells from MS patients than on CD4+ lymphocytes from controls (434 +/- 11 vs. 363 +/- 9 (mean +/- SEM) receptors/cell, respectively); CD8+ T cells showed very few IL-6 receptors in both patients and controls. These data are discussed in terms of MS immune pathogenesis and pathophysiology, because T-cell activation seems to be linked to increased IL-6 binding. The upregulated IL-6 system might be involved in antibody-mediated demyelinating pathways, because IL-6 is well known to enhance humoral immune response.

Increase in Interleukin-6 Levels Is Related to Depressive Phenomena in the Acute (Relapsing) Phase of Multiple Sclerosis

“…The upregulated IL-6 system is involved in antibody-mediated demyelinating pathways, because IL-6 is well known to enhance humoral immune response. 5 IL-6 is predominantly located at the sites of ongoing demyelination and immune activation.…”

“…16,17 IL-6, as one of the most widely investigated pro-inflammatory cytokine, was used by a great number of researchers as a reliable biomarker in both MS and depression literature. [5][6][7]10,12 Many researchers indicate a possible correlation between IL-6 and MS, as well as between IL-6 and depression, but the possible correlation among the acute phase of MS, IL-6, and depression is not well investigated, maybe because depression is underdiagnosed, particularly during this phase of MS. The investigation of IL-6 and its soluble receptor may broaden the basis of understanding the underlying mechanisms of depression and the different phases of MS, and may therefore contribute to its treatment.…”

Although IL-6 Trans-Signaling Is Sufficient To Drive Local Immune Responses, Classical IL-6 Signaling Is Obligate for the Induction of T Cell-Mediated Autoimmunity

“…A central role for IL-6 also has been described for the generation of the GC reaction, Ig somatic hypermutation, affinity maturation (5,32), and plasma cell differentiation (33). In autoimmunity, inflammation driven by IL-6 is often the hallmark of the pathophysiology associated with diseases, such as RA, multiple sclerosis, and inflammatory bowel disease (7,19,28,(34)(35)(36). Animal models of these human conditions have demonstrated a role for IL-6 in the generation of autoimmune T cells (in particular Th17) and humoral responses leading to joint destruction in CIA (34), brain lesions in experimental autoimmune encephalitis (37,38), and gut inflammation in intestinal bowel disease (7).…”

Immunomodulatory properties of the IL‐6 cytokine family in multiple sclerosis

“…The immune modulatory effects of the cytokines are of course determined by the expression of the respective receptor subunits on different immune cells. The receptor for IL‐6 is enhanced on circulating CD4 + T cells of MS patients, and LIFRβ is strongly upregulated on circulating T cells, B cells, and macrophages of untreated MS patients . Moreover, in lesions of MS patients, macrophages/microglia express the LIFRβ, as well as perivascular T cells .…”