Intrapleural therapy with MDP-Lys (L18), a synthetic derivative of muramyl dipeptide, against malignant pleurisy associated with lung cancer.
N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys (L18), romurtide) is a synthetic muramyl dipeptide derivative, and has immunomodulating activities including activation of cells of monocyte-macrophage lineage. We examined the effect of intrapleural instillation of MDP-Lys (L18) against malignant pleurisy associated with lung cancer. Six patients with cytologically-positive malignant pleural effusion (four with adenocarcinoma, one with small cell carcinoma and one with large cell carcinoma) were treated with single intrapleural instillation of MDP-Lys (L18) of 200 microg. Clinically, no reaccumulation of pleural effusion for at least 4 weeks was observed in four patients. No major side effects were observed. Total cell number elevated remarkably 4 h after instillation, and main increased population was that of neutrophils. Levels of chemotactic cytokines, such as interleukin (IL)-8, and monocyte chemotactic protein (MCP)-1 and levels of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, elevated in pleural effusion, and peak IL-1beta and IL-6 levels tended to be higher in clinical responders than non-responders. These results suggest MDP-Lys (L18) instilled by intrapleural route had a potential local immunomodulatory activity. Further study is warranted to further determine the critical factors which correlate with the clinical response.
Yanagawa
H
H
The University of Tokushima, School of Medicine, Third Department of Internal Medicine, Japan. niseko@clin.med.tokushima-u.ac.jp
Haku
T
T
Takeuchi
E
E
Suzuki
Y
Y
Nokihara
H
H
Sone
S
S
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D016207:Cytokines / Q000187:drug effects / Q000494:pharmacology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications*; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000209:etiology; D010998:Pleurisy / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016207:Cytokines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide