title: Modulation of inflammatory response in mice with severe autoimmune disease by thymic peptide thymulin and an inhibitor of NF-kappaB signalling.
abstract: To investigate some cellular and molecular aspects of the autoimmune response and anti-inflammatory efficiency of potential therapeutic agents in a severe form of experimental autoimmune encephalomyelitis (sEAE), an inhibitor of NF-kappaB signalling, IKK Inhibitor XII, and/or thymic peptide thymulin, were injected intraperitoneally at 1.8 and 0.15mg/kg e.o.d, respectively, to C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein and several adjuvants. The immunization induced high lethality in three weeks. The biphasic cytokine response observed in earlier and delayed phases was attributed to the activity of Th1 and Th17 cells, respectively. Phosphorylation of RelA protein from the NF-kappaB family increased during the earlier phase and decreased in the delayed phase. SAPK/JNK signalling protein and heat shock protein Hsp72 significantly increased in lymphocytes. Both the IKK Inhibitor XII and thymulin reduced disease severity, attenuated immune imbalance, and increased mouse life-span. Co-administration of the agents produced no additive effect. Both the inhibitor and thymulin reduced the Th1 response but not the Th17 response. Therefore, RelA-associated Th1 activation and RelA-independent Th17 activation occurred in sEAE. Thymulin and the inhibitor demonstrate similar patterns of activity, potentially through the RelA pathway inhibition, resulting in a partial therapeutic effect on the animals' health status.
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia. Electronic address: lunin@pochta.ru.
authors: S M
authors: SM
authors: Lunin
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia.
authors: M O
authors: MO
authors: Khrenov
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia.
authors: T V
authors: TV
authors: Novoselova
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia.
authors: S B
authors: SB
authors: Parfenyuk
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia.
authors: O V
authors: OV
authors: Glushkova
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia.
authors: E E
authors: EE
authors: Fesenko
authors: Institute of Cell Biophysics, Russian Academy of Sciences, Russia.
authors: E G
authors: EG
authors: Novoselova
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D050884:HSP72 Heat-Shock Proteins / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013935:Thymic Factor, Circulating / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D050884:HSP72 Heat-Shock Proteins; D016328:NF-kappa B; D013935:Thymic Factor, Circulating; D020928:Mitogen-Activated Protein Kinases
keywords: Autoimmune diseases; IKK inhibitor XII; Interferon-gamma; Interleukin-17; NF-kappaB; Thymulin