Effect of praziquantel and liposome-incorporated praziquantel on peritoneal macrophage activation in mice infected with Mesocestoides corti tetrathyridia (Cestoda).
The activation of peritoneal macrophage effector functions after therapy with free PZQ and PZQ incorporated in liposomes (lip.PZQ) was studied in the Mesocestoides corti-mouse model system. Each drug formulation was administered to an infected group of mice in 6 daily doses from day 14 p.i. Phagocytic activity of macrophages increased significantly after the administration of both drug formulations, more after lip.PZQ with an earlier peak observed for PZQ (day 3) than for lip.PZQ (day 6). Empty liposomes had no significant effect. The average counts of ingested particles in phagocytosing cells were significantly higher only after lip.PZQ administration. The pattern of changes in phagocytic activity correlated with the reduction of parasite numbers in the peritoneal cavity, with the highest observed on day 6 after therapy with lip.PZQ. Phagocytosis of lip.PZQ in vivo stimulated significantly the respiratory burst in peritoneal macrophages, with the highest concentration of superoxide anions recorded on day 1 after the last dose, whereas therapy with PZQ itself did not increase this process significantly. The capacity for the respiratory burst declined in all groups with progressing infection. It is proposed that the phagocytic activity of peritoneal macrophages after therapy was stimulated indirectly as a consequence of activation of the specific immune response. The larvicidal effect of lip.PZQ on the tetrathyridia in the peritoneal cavity was synergistic with the phagocytic activity and might be the result of double action of drug and superoxide anions generated during the respiratory burst stimulated by this drug formulation.
Hrckova
G
G
Parasitological Institute, Slovak Academy of Sciences, Kosice, Slovak Republic. hrcka@linux1.saske.sk
Velebny
S
S
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002590:Cestode Infections / Q000188:drug therapy / Q000276:immunology*; D004337:Drug Carriers; D007814:Larva / Q000187:drug effects; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008645:Mesocestoides / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D010529:Peritoneal Cavity / Q000469:parasitology; D010587:Phagocytosis; D011223:Praziquantel / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016897:Respiratory Burst
D000980:Antiplatyhelmintic Agents; D004337:Drug Carriers; D008081:Liposomes; D011223:Praziquantel