15d-PGJ(2) modulates acute immune responses to Trypanosoma cruzi infection.
The acute phase of Trypanosoma cruzi infection is associated with a strong inflammatory reaction in the heart characterised by a massive infiltration of immune cells that is dependent on the T. cruzi strain and the host response. 15d-PGJ(2) belongs to a new class of anti-inflammatory compounds with possible clinical applications. We evaluated the effects of 15d-PGJ(2) administered during the acute phase of T. cruzi infection in mice. Mice were infected with the Colombian strain of T. cruzi and subsequently treated with 15d-PGJ2 repeatedly for seven days. The inflammatory infiltrate was examined by histologic analysis. Slides were immunohistochemically stained to count the number and the relative size of parasite nests. Infection-induced changes in serum cytokine levels were measured by ELISA. The results demonstrated that treatment with 15d-PGJ(2) reduced the inflammatory infiltrate in the skeletal muscle at the site of infection and decreased the number of lymphocytes and neutrophils in the blood. In addition, we found that 15d-PGJ(2) led to a decrease in the relative volume density of amastigote nests in cardiac muscle. T. cruzi-infected animals treated with 15d-PGJ(2) displayed a statistically significant increase in IL-10 levels with no change in IFN-gamma levels. Taken together, we demonstrate that treatment with 15d-PGJ(2) in the acute phase of Chagas disease led to a controlled immune response with decreased numbers of amastigote nests, as measured by the volume density.
Rodrigues
Wellington F
WF
Laboratório de Biopatologia e Biologia Molecular, Universidade de Uberaba, Uberaba, MG, Brasil.
Miguel
Camila B
CB
Chica
Javier E Lazo
JE
Napimoga
Marcelo H
MH
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists* / Q000627:therapeutic use; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use
C477819:15-deoxyprostaglandin J2; D047495:PPAR gamma; D016753:Interleukin-10; D007371:Interferon-gamma; D015230:Prostaglandin D2