A biochemical study of the phagocytic activities of tuftsin and its analogues.

Abstract

The effects of tuftsin and one of its analogues (4 [lys]-tuftsin) on phagocytosis of Staphylococcus aureus and Candida albicans were investigated in mice and rabbits. Mice were intravenously or orally administered 1-25 mg of 4 [lys]-tuftsin per kg daily for 4 to 7 days. After the mice were further treated with cyclophosphamide, they were intravenously challenged with C. albicans. More than 50% of the mice infected with C. albicans were killed within 7 days, although only 20% to 40% of those infected with the same microbes after 4 [lys]-tuftsin treatment died. A combination of 4 [lys]-tuftsin and an antibiotic was found to be somewhat more effective than either one alone. Further, pretreatment with 4 [lys]-tuftsin depressed microbial growth in the kidneys of mice bearing S-180 tumors. Rabbit peritoneal macrophages and polymorphonuclear leukocytes were harvested by intraperitoneal injection of liquid paraffin and of glycogen solution, respectively. For in vitro study of phagocytosis, rabbit macrophages of polymorphonuclear leukocytes were incubated in Hanks solution together with S. aureus and the number of survivors was determined. Enhanced engulfing activity of macrophages and increased bactericidal activity of polymorphonuclear leukocytes were shown by the in vitro phagocytosis experiments. It is expected that 4 [lys]-tuftsin will be effective against infectious disease, especially in immunocompromised hosts such as patients with malignant tumors.