Effect of MDP-Lys(L18), a derivative of MDP, on enhancing host resistance against Hantaan virus infection in newborn mice.
We examined the effect of MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, on the enhancement of host resistance against virus infection in newborn mice. Newborn mice were inoculated with 4 LD50/mouse of Hantaan virus strain 76-118 (HTN) one day after birth. Mice given 100 micrograms/mouse of MDP-Lys(L18) before infection exhibited significantly higher survival rates than those of non-treated mice. The effect of MDP-Lys(L18) was also restorative when given to the mice 4 or 7 days after infection. The titers of virus isolated from the lungs and spleens 12 days after infection, were about 30-times lower in MDP-Lys(L18)-treated (lung: 1.0 x 10(3) FFU; spleen: 6.8 x 10(1) FFU/mouse), than those of non-treated mice (lung: 3.4 x 10(4) FFU; spleen: 1.9 x 10(3) FFU/mouse). Furthermore, the virus was undetectable in the brains of MDP-Lys(L18)-treated mice, whereas viruses were isolated from 3 of 6 non-treated mice. MDP-Lys(L18) augmented the number of peripheral leukocytes and splenocytes, as well as mitogenic responses of the cells from bone marrow and spleen of newborn mice. These results suggest that MDP-Lys(L18) enhanced the resistance of newborn mice against HTN virus in a systemic infection model, and that this mechanism is involved in the enhancement of hematopoiesis and responsiveness of immune-related cells to mitogens.
Yoo
Y C
YC
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Yoshimatsu
K
K
Hatsuse
R
R
Tamura
M
M
Yoshida
R
R
Tono-oka
S
S
Arikawa
J
J
Azuma
I
I
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D001921:Brain / Q000821:virology; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D018063:Hantaan virus; D006410:Hematopoiesis / Q000187:drug effects; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology* / Q000517:prevention & control; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000821:virology
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D003208:Concanavalin A; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide