The possible role of interleukin (IL)-12 and interferon-gamma-inducing factor/IL-18 in protection against experimental Mycobacterium leprae infection in mice.
Cell-mediated immunity participates in host defense against mycobacterial infection. Both interleukin 12 (IL-12) and interferon-gamma-inducing factor (IGIF/IL-18), produced mainly by macrophages, play a critical role in expression of cell-mediated immunity. To investigate the role of IL-12 and IGIF/IL-18 in vivo, we examined cytokine profile, bacterial growth, and the potential benefit of cytokine therapy in susceptible and resistant mice infected with Mycobacterium leprae. The early expression of IL-12 p40 and IGIF/IL-18 at the site of inoculation was found in resistant mice 3-72 h after the infection, but not in susceptible mice. Both strains of mice did not show expression of IFN-gamma and IL-4. IL-12 administration resulted in a significant reduction of bacterial counts in mice with established M. leprae infection. The results imply that susceptible mice exhibit decreased expression of type 1 helper T (Th1) response without reciprocal increased Th2 response and show responsiveness to exogenous IL-12. IL-12 therapy may be a possible rationale for treatment of M. leprae infection.
Kobayashi
K
K
Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama-shi, Tokyo, 189-0002, Japan. kobayak@nih.go.jp
Kai
M
M
Gidoh
M
M
Nakata
N
N
Endoh
M
M
Singh
R P
RP
Kasama
T
T
Saito
H
H
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007113:Immunity, Innate / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D020382:Interleukin-18; D007918:Leprosy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009166:Mycobacterium leprae; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12