PMID- 19344957 OWN - NLM STAT- MEDLINE DCOM- 20090706 LR - 20211203 IS - 1872-8421 (Electronic) IS - 0165-5728 (Linking) VI - 210 IP - 1-2 DP - 2009 May 29 TI - Combined treatment with minocycline and prednisone attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice. PG - 22-9 LID - 10.1016/j.jneuroim.2009.02.016 [doi] AB - There has been enormous progress in the treatment of multiple sclerosis (MS) in recent years, but further improvement in therapy is still required because not all patients respond optimally to existing treatments. Increasing evidence has demonstrated that combination therapies produce a more favorable clinical outcome than monotherapy in MS treatment. Minocycline is effective in experimental autoimmune encephalomyelitis (EAE), and is a promising candidate for future MS medication. Glucocorticosteroids (GCS) belong to the most potent immunosuppressive drugs and are the mainstay for treatment of acute relapses in MS. In this study, we tested whether the combination of minocycline and prednisone (a synthetic GCS) at suboptimal doses could produce synergistic effects in EAE. Our findings showed that the combination of these two drugs functioned better than when they were individually administered in EAE mice, as evidenced by decreased clinical scores, reduced inflammation and demyelination, and improved magnetic resonance imaging outcomes. Further studies revealed that the combined treatment prevented the reduction of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNA expression in cerebral cortex of EAE mice. In conclusion, our findings indicated that this combination therapy suppressed disease severity of EAE partially through blocking the downregulation of neurotrophic factor expression, suggesting that the combination of minocycline and prednisone could be a novel treatment in MS. FAU - Chen, Xiaohong AU - Chen X AD - Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Hu, Xueqiang AU - Hu X FAU - Zou, Yan AU - Zou Y FAU - Pi, Rongbiao AU - Pi R FAU - Liu, Mei AU - Liu M FAU - Wang, Tieqiao AU - Wang T FAU - Zheng, Xueping AU - Zheng X FAU - Liu, Meng AU - Liu M FAU - Lin, Mingdong AU - Lin M FAU - Liu, Peiqing AU - Liu P FAU - Tao, Liang AU - Tao L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090402 PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (Anti-Bacterial Agents) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 9061-61-4 (Nerve Growth Factor) RN - FYY3R43WGO (Minocycline) RN - VB0R961HZT (Prednisone) SB - IM EIN - J Neuroimmunol. 2009 Oct 30;215(1-2):130 MH - Animals MH - Anti-Bacterial Agents/pharmacology/therapeutic use MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Brain-Derived Neurotrophic Factor/genetics MH - Central Nervous System/drug effects/immunology/pathology MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects/immunology MH - Drug Therapy, Combination MH - Encephalomyelitis, Autoimmune, Experimental/*drug therapy/immunology/physiopathology MH - Female MH - Immunosuppression Therapy/*methods MH - Magnetic Resonance Imaging MH - Mice MH - Mice, Inbred C57BL MH - Minocycline/*pharmacology/therapeutic use MH - Nerve Fibers, Myelinated/drug effects/immunology/pathology MH - Nerve Growth Factor/genetics MH - Prednisone/*pharmacology/therapeutic use MH - RNA, Messenger/drug effects/metabolism MH - Treatment Outcome EDAT- 2009/04/07 09:00 MHDA- 2009/07/07 09:00 CRDT- 2009/04/07 09:00 PHST- 2008/12/22 00:00 [received] PHST- 2009/02/13 00:00 [revised] PHST- 2009/02/18 00:00 [accepted] PHST- 2009/04/07 09:00 [entrez] PHST- 2009/04/07 09:00 [pubmed] PHST- 2009/07/07 09:00 [medline] AID - S0165-5728(09)00070-8 [pii] AID - 10.1016/j.jneuroim.2009.02.016 [doi] PST - ppublish SO - J Neuroimmunol. 2009 May 29;210(1-2):22-9. doi: 10.1016/j.jneuroim.2009.02.016. Epub 2009 Apr 2.