Mast-cell-dependent histamine release after praziquantel treatment of Schistosoma japonicum infection: implications for chemotherapy-related adverse effects.
As previously shown, the development of adverse effects in praziquantel treatment of Schistosoma japonicum infection involves host anaphylactic reactions associated with a rapid elevation of the level of plasma histamine. This study, using genetically mast-cell-deficient mice, aimed at identifying the major source of plasma histamine released after praziquantel treatment. Mast-cell-deficient mice and congenic normal mice were treated with praziquantel 8 weeks after infection with S. japonicum. In normal congenic mice, the plasma histamine level at 60 min after chemotherapy was substantially higher (mean+/-SD: 123.34+/-23.13 ng/ml) than that in mast-cell-deficient mice (7.02+/-3.48 ng/ml). These results show that mast cells play a predominant role in the rapid increase of the plasma histamine level. Despite their lack of increase in plasma histamine, mast-cell-deficient mice exhibited post-praziquantel systemic signs but not histopathologic alterations due to allergic reactions, suggesting that unidentified mechanism(s) also contribute to the development of adverse post-praziquantel effects.
Matsumoto
Jun
J
Department of Tropical Medicine and Parasitology, Dokkyo University School of Medicine, Mibu, Shimotsuga, Tochigi, 321-0293 Japan. junmatsu@dokkyomed.ac.jp
Matsuda
Hajime
H
D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006636:Histamine Release; D006651:Histocytochemistry; D007073:Immunoglobulin E / Q000032:analysis; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008813:Mice, Inbred ICR; D011223:Praziquantel / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012549:Schistosoma japonicum / Q000187:drug effects; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D000871:Anthelmintics; D007073:Immunoglobulin E; D011223:Praziquantel