Induction of tumoricidal macrophages and production of cytokines by synthetic muramyl dipeptide analogues.
The ability of various synthetic muramyl dipeptide (MDP) derivatives to induce the production of interleukin-1 (IL-1) and colony stimulating factor (CSF) in vitro and in vivo and to induce cytotoxic macrophages was studied. 6-O-L18-MDP(Me) and MDP-Lys(L18), which were potent inducers of IL-1 and CSF production and of cytotoxic macrophages, had protective activity against Sendai virus infection in mice. In contrast, 1-O-L18-(6-O-P)-MDP(Me) and 2-N-L18-MDP exhibited weak or no ability to induce IL-1 and CSF production and no induction of tumoricidal macrophages, and did not protect against infection of Sendai virus. MDP derivatives, except 2-N-L18-MDP, efficiently rendered macrophages cytotoxic against target cells in the presence of murine recombinant interferon-gamma in vitro. The derivatives that induced cytokines and cytotoxic macrophages appeared to produce anti-viral activity.
Saiki
I
I
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Saito
S
S
Fujita
C
C
Ishida
H
H
Iida
J
J
Murata
J
J
Hasegawa
A
A
Azuma
I
I
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis*; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018184:Paramyxoviridae Infections / Q000517:prevention & control; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000276:immunology
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine