Diacerhein downregulate proinflammatory cytokines expression and decrease the autoimmune diabetes frequency in nonobese diabetic (NOD) mice.
NOD mice are used as experimental models as they develop type 1 diabetes mellitus (DM-1) spontaneously, with a strong similarity to the human disease. Diabetes mellitus type 1 is characterized by the destruction of the islet, orchestrated by T lymphocytes that induce cytokine release like IL-1beta, promoting an inflammatory process. Diacerhein has antiinflammatory properties, inhibiting IL-1. However, the mechanisms involved in immune modulation are not completely understood. In the present study, serum and pancreatic islets were isolated to investigate the relationship between IL-1beta, IFN-gamma, IL-12 and TNF-alpha expression and diabetes onset, morphological aspects, and diacerhein dose dependence in animals treated with different doses (5, 10 and 50 mg/kg/day) and the control group (saline solution). The results demonstrated upregulation of mRNA islets and downregulation of the serum concentration of IL-1beta, IL-12 and TNF-alpha in the group treated with 5 and 10 mg/kg/day diacerhein, when compared with the saline group, and increased IFN-gamma serum concentration in the group treated with 50 mg/kg/day. These results suggest that diacerhein in NOD mice, decreases, in a dose-dependent manner, the diabetes frequency downregulating proinflammatory cytokines, such as IL-1beta, TNF-alpha, IFN-gamma and IL-12 at posttranscriptional or posttranslational level. Furthermore, using the HPLC method, diacerhein and rhein (active metabolite) were detected in serum and pancreas of treated mice.
Malaguti
Carina
C
Laboratory of Immunology & Experimental Allergy - Department of Internal Medicine, School of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
Vilella
Conceição Aparecida
CA
Vieira
Karla Priscila
KP
Souza
Gustavo H M F
GH
Hyslop
Stephen
S
Zollner
Ricardo de Lima
Rde L
D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects / Q000378:metabolism
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C025292:diacerein; D007371:Interferon-gamma