High interleukin-10 expression within the central nervous system may be important for initiation of recovery of Dark Agouti rats from experimental autoimmune encephalomyelitis

Abstract

Dark Agouti (DA) rats are highly susceptible to induction of experimental autoimmune encephalomyelitis (EAE), still they completely recover from the disease. Here, we were interested to determine contribution of major anti-inflammatory cytokines transforming growth factor (TGF)-β and interleukin (IL)-10 to the recovery of DA rats from EAE. To that extent we determined CNS expression of these cytokines in DA rats at different phases of EAE and compared data to those obtained in EAE-resistant Albino Oxford (AO) rats. Higher expression of TGF-β was persistently observed in the CNS of AO rats, even if rats were not immunized. This implied that high TGF-β within the CNS is important for resistance of AO rats to EAE induction. On the contrary, IL-10 expression was consistently higher in DA than in AO rats and it culminated at the peak of EAE. Methylprednisolone suppressed EAE and expression of IL-10 in spinal cord homogenates, while IL-10 was increased in CNS-infiltrating immune cells. This implied that IL-10 might have a significant role in recovery of DA rats from the disease. Thus, we next explored effects of IL-10 on astrocytes, glial cells that largely contribute to control of CNS inflammation. IL-10 stimulated astrocytic expression of an important regulator of neuroinflammation, CXCL12. Thus, IL-10 might contribute to recovery of DA rats from EAE through induction of CXCL12 expression in astrocytes.

Keywords: AO; Albino Oxford; Astrocyte; CFA; CNS; CXCL12; ConA; ConASn; DA; DLN; DLNC; Dark Agouti; EAE; Experimental autoimmune encephalomyelitis; IFA; IFN; IL; Interleukin-10; MBP; MOG; MP; MS; Neuroinflammation; PBMC; PBS; SC; SCH; TGF; Th; Transforming growth factor; c.s.; cell free supernatant collected from 48h culture of rat splenocytes stimulated with ConA; central nervous system; clinical score; complete Freund's adjuvant; concanavaline A; d.p.i.; days post immunization; draining lymph node; draining lymph node cells; experimental autoimmune encephalomyelitis; helper T cells; incomplete Freund's adjuvant; interferon; interleukin; methylprednisolone; multiple sclerosis; myelin basic protein; myelin oligodendrocyte protein; peripheral blood mononuclear cells; phosphate buffer saline; spinal cord; spinal cord homogenate; transforming growth factor.