This study was carried out in mice experimentally immunocompromised with various immunosuppressants to clarify the host defense mechanism against microbial infection and to investigate the usefulness of immunopotentiators against infection.
Host defense against extracellular and facultative intracellular pathogens including
Pseudomonas aeruginosa and
Listeria monocytogenes was markedly reduced in cyclophosphamide-, hydrocortisone-, carrageenan- and mitomycin C-treated mice. In particular, the action of cyclophosphamide and hydrocortisone on phagocytes weres different: cyclophosphamide markedly reduced the count of phagocytes including PMN leucocytes and macrophages, whereas hydrocortisone markedly reduced phagocyte functions such as chemotaxis of PMN leucocytes and phagocytosis and intracellular killing by macrophages.
Additionally, the relationship between phagocytosis and intracellular killing of peritoneal phagocytes against
P. aeruginosa and
Candida parapsilosis and host defense against
P. aeruginosa infection were studied in mice given various immunopotentiators. (D)-lactoyl-(L)-alanyl-γ-(D)-glutamyl-(L)-meso-diaminopimelyl-(L)-glycine, an immunoactive tetrapeptide (IATP), was the most active of all the immunopotentiators in normal mice, and restored host defense against various microbial infection in immunocompromised mice by increasing the phagocyte count and enhancing the phagocyte function. The protective effect of gentamicin and ticarcillin in combination with IATP was synergistic against
P. aeruginosa infection in immunocompromised mice. This suggests that immunopotentiators bring about restoration of host defense in the immunocompromised host and play an important role in the treatment of intractable infection when used in combination with antibiotics.
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