[1, 25-dihydroxyvitamin D3 promotes the apoptosis of inflammatory cells in acute experimental autoimmune encephalomyelitis: experiment with rats].
OBJECTIVE
To investigate the mechanism of rapid amelioration of the pathological changes in experimental allergic encephalomyelitis (EAE) by 1, 25-dihydroxyvitamin D(3) [1, 25-(OH)(2)D(3)].


METHODS
Forty Lewis rats were immunized with myelin basic protein in complete Freud's adjuvant so as to establish ESE animal models and then randomly divided into 4 equal groups: prevention group, fed with 1, 25-(OH)(2)D(3) since day 0 for 10 days, prevention-control group fed with peanut oil for 10 days, treatment group fed with 1, 25-(OH)(2)D(3) since the appearance of EAE symptoms (generally since day 10 or 11), and treatment-control group fed with peanut oil since the appearance of EAE symptoms. The clinical symptoms were scored since immunization till day 12 when the clinical symptoms reached the maximum level. The rats were sacrificed 13 days after sensitization with their brains and spinal cords taken out to undergo pathological examination, in situ TUNEL staining for detecting apoptotic cells, and semiquantitative immunohistochemical analysis to detect the inducible NO synthase (iNOS), FasL, and tumor growth factor (TGF)-beta 1, that might involve in the signal pathway of apoptosis. Peripheral blood samples were collected to isolate mononuclear cells (MNCs). The content of nitrite in the supernatant of MNC culture was evaluated.


RESULTS
The scores of clinical symptoms and the pathological changes of both the prevention and treatment groups decreased conspicuously and were significantly lower than their respective control groups (both P < 0.01). In contrast, the apoptosis indexes of the 2 1, 25-(OH)(2)D(3) administration groups were significantly higher than those of the control groups (all P < 0.01). The TUNEL positive cell rates in the brain and spinal cord of the treatment and prevention groups were all significantly higher than those of their corresponding control groups (P < 0.05, P < 0.01). The numbers of iNOS positive cells in the treatment and prevention groups were both lower than those of their corresponding control groups, which was in accord with the improvement of clinical signs and tissue lesions. The levels of nitrite in the supernatant of MNC culture of the treatment and prevention groups were higher than those of their corresponding control groups, but not significantly.


CONCLUSIONS
Administration of 1, 25-(OH)(2)D(3) rapidly ameliorates EAE symptoms by promoting the apoptosis of inflammatory cells. The elimination of infiltrating immune cells which reverses the pathological changes in central nervous system is associated with a favorable microenvironment provided by 1, 25-(OH)(2)D(3), such as decreasing of iNOS.
Jiao
Zhuo-Min
ZM
Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. zm.jiao@yahoo.com.cn
Fu
Yu-Hong
YH
Fu
Jin
J
Zhang
Feng
F
Wang
Wei-Zhi
WZ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000473:pathology; D005260:Female; D051381:Rats; D011917:Rats, Inbred Lew; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
C118756:dihydroxy-vitamin D3; D014807:Vitamin D