Arthritis and hematological changes induced by an analogue of muramyl dipeptide in rats.
We examined changes of blood cell counts and development of arthritis induced by daily subcutaneous injections of MDP-Lys(L18), an analogue of muramyl dipeptide (MDP), in rats. The numbers of neutrophils markedly increased in the peripheral blood 4 hr after the 1st, 7th, and 14th administrations of MDP-Lys(L18), but they recovered to the control levels within 24 hr. Monocyte and lymphocyte counts increased after the 7th and 14th administrations, respectively, although both decreased after the 1st dosing. Serum inflammatory markers, such as albumin, globulin, mucoprotein, sialic acid, and iron, showed marked changes after the 1st administration. Histopathologically, the synovial membrane of the tarsal joint showed a multilayer arrangement of synoviocytes with vesicular cytoplasms and infiltration of neutrophils from 6 hr after the 1st administration of the drug. The acute synovitis was gradually enhanced until 24 hr later. The synovitis was greatly decreased in degree after the 3rd administration, but increased again later. After the 7th and 14th administrations, mononuclear cells and lymphocytes, respectively, infiltrated the synovial membrane, in a manner corresponding to the hematological findings. However, exudative changes and neutrophilic infiltration were still observed after the 14th drug administration, and the synovitis was repaired after a 7-day recovery period.
Sugawara
T
T
Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Kato
M
M
Takayama
S
S
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D005260:Female; D007958:Leukocyte Count; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013583:Synovial Membrane / Q000473:pathology; D013640:Tarsal Joints / Q000473:pathology; D013997:Time Factors
D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide