Potential use of tuftsin in treatment of candida peritonitis in a murine model.
A major complication of continuous ambulatory peritoneal dialysis (CAPD) is peritonitis caused by Candida albicans. Increasing the activity of the peritoneal macrophages, the predominant cell type found in the peritoneal cavity, may be a promising treatment for this infection. Tuftsin was found to increase thioglycollate-elicited mouse peritoneal macrophage activity. 2x10(-7) M tuftsin enhanced two-fold cell association with radiolabelled candida, superoxide aniom production, and killing activity. Thus, a model consisting of mice undergoing peritoneal dialysis was developed in order to study the use of tuftsin as a therapeutic drug against peritoneal candidiasis. Administration of tuftsin (50 micrograms/mouse) before candidiasis induction with a lethal dose of candida (7x10(8) candida per mouse) improved mouse survival up to 70%, compared with 10% in the control group. The potential of tuftsin as a treatment for candidiasis was shown when the infection was induced with a sublethal dose of candida. Daily intraperitoneal injections of tuftsin (50 micrograms) to the sublethally infected mice caused a significant decrease in the number of candida recovered from the peritoneal cavity and from the blood (from 700 +/- 190 to 110 +/- 26 CFU/ml and from 100 +/- 26 CFU/ml to 17 +/- 8 CFU/ml, respectively). In addition, a larger number of peritoneal macrophages with greater phagocytic and killing activity were found in the tuftsin-treated mice. The effect of tuftsin may promote its potential use in the therapy of peritonitis in patients undergoing chronic peritoneal dialysis.
Levy
R
R
Institute of Infectious Diseases, Weizmann Institute of Science, Rehovot, Israel.
Kain
Z
Z
Chaimovitz
C
C
Fridkin
M
M
Segal
S
S
Alkan
M
M
D000818:Animals; D002176:Candida albicans / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy*; D002452:Cell Count; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000166:cytology; D010530:Peritoneal Dialysis; D010538:Peritonitis / Q000188:drug therapy*; D010587:Phagocytosis; D013481:Superoxides / Q000032:analysis; D013997:Time Factors; D014405:Tuftsin / Q000627:therapeutic use*
D013481:Superoxides; D014405:Tuftsin