Effect of apolipoprotein E on inflammation in mice with experimental autoimmune encephalomyelitis

Objective To explore the effect of apolipoprotein E (ApoE) on expressions of interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF)-α in central nervous system of mice with experimental autoimmune encephalomyelitis (EAE). Methods Ten C57BL/6J ApoE-deficient (ApoE-/-) mice were selected randomly as ApoE-/- group; 40 normal C57BL/6J mice were randomly divided into wild-type (WT) group, peptide (COG1120)-treated group, vehicle group and normal control group (n=10), and mice in the ApoE-/- group, WT group, COG1120-treated group and vehicle group were injected with completeantigen (MOG35-55 in an PBS buffer with complete Freund adjuvant containing Bacillus Calmette-Guerin vaccine) to induce EAE models. Mile in normal control group were not induced EAE models. Mice of COG1120-treated group were injected subcutaneously with COG112 (5 mg/kg body weight in saline) every two days from day 2 to day 35 post- immunization. Mice of vehicle group were injected with physiological saline instead of COG112. Neurological severity scale scores from day 0 to day 35 were recorded. On day 35 after immunization, mice were sacrificed; spinal cord and brain tissues were harvested; the inflammatory infiltration was observed through HE staining; the expressions of IL-17, IL-6 and TNF-α were quantified by immunohistochemistry. Results The peak symptoms at neurological severity scale and degrees of inflammatory cell infiltration in ApoE-/- group were significantly worse than those in WT group (P<0.05). The average optical density of IL-17, IL-6 and TNF-α in the ApoE-/- group, WT group, COG1120-treated group and vehicle group was significantly higher than that in the normal control group (P<0.05); that in the ApoE-/- group was significantly higher than that in the WT group (P<0.05); that in the COG1120-treated group and was significantly higher than that in the vehicle group (P<0.05). Conclusions ApoE deficiency in the EAE mile could enhance inflammatory infiltrates into CNS, and increase the levels of IL-17, IL-6 and TNF-α in CNS. After the ApoE peptide treatment, the levels of IL-17, IL-6 and TNF-α in CNS decrease, therefore, ApoE and COG112 in EAE mile may play a protective role. Key words: Experimental autoimmune encephalomyelitis; Apolipoprotein E; Interleukin 17; Interleukin 6; Tumor necrosis factor-α