Cytokines and soluble IL‐4 in patients with acute optic neuritis and multiple sclerosis

Abstract

We measured the cerebrospinal fluid (CSF) and plasma concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, TNF-β, interferon (IFN)-γ, the IL-1 receptor antagonist, and soluble IL-4 receptor (sIL-4r) by ELISA in 12 patients each with acute, monosymptomatic, idiopathic optic neuritis (ON), ON as part of MS, other attack forms of MS, and in neurological control subjects. CSF concentrations of IL-1β, IL-2 and IFN-γ differed significantly between the different patient groups and were detected most commonly at the highest concentrations in patients with non-ON attacks of MS. TNF-β was detected exclusively in CSF from neurological control patients. The patients with non-ON attacks of MS also had significantly elevated concentrations of sIL-4r in plasma. Increased CSF concentrations of IL-1β, IL-2 and IFN-γ together with increased plasma concentrations of sIL-4r support the concept of MS as an autoimmune disease with preferential activation of proinflammatory or T-helper type 1-like cells. Patients with idiopathic ON or ON as part of MS may, however, differ immunologically from patients with other attack forms of MS.

Protease-activated receptor-1 activation by granzyme B causes neurotoxicity that is augmented by interleukin-1β

“…Previous research has demonstrated that CSF from patients with MS is directly toxic to cultured rat neurons [29]. The CSF of patients with MS contains abundant granzyme B [18] and IL-1β [19, 30], and CSF IL-1β concentrations correlate with MS-associated brain atrophy [22]. Our research shows that persistent granzyme B drives neurotoxicity and IL-1β augments neuronal death by increasing PAR1 expression.…”

“…IL-1β circulating within the cerebrospinal fluid (CSF) is a biomarker of neuroinflammation caused by MS [19] and subacute sclerosing panencephalitis [20]. IL-1β augments neuronal excitotoxicity [21].…”

Immunological effects of oral high‐dose methylprednisolone in acute optic neuritis and multiple sclerosis

“…In contrast, IL-10 and TGF-b may attenuate immunological and, hence, clinical disease activity (Sùrensen and Ransohoff, 1998). We did not detect TNF-a or IL-10 in cerebrospinal fluid but this may reflect recognized technical difficulties in measuring cytokines in body fluids (Sharief and Hentges, 1991;Sellebjerg et al, 1997). Methylprednisolone-induced decreases in the serum concentration and blood mononuclear cell expression of TNF-a, and treatment-induced increases in the serum concentration and blood mononuclear cell expression of IL-10 were recently reported (Pitzalis et al, 1997;Gayo et al, 1998;Wandinger et al, 1998).…”