In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis.
Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 microgram of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis-induced spleen T cell proliferative responses as well as IFN-gamma and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 microgram of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-gamma production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis.
Emery
I
I
Laboratorie de Parasitologie, Faculté de Médecine, Créteil, France.
Leclerc
C
C
Sengphommachanh
K
K
Vuitton
D A
DA
Liance
M
M
D000818:Animals; D004444:Echinococcosis, Hepatic / Q000276:immunology / Q000628:therapy*; D004446:Echinococcus / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins
D007376:Interleukin-2; D015848:Interleukin-5; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma