Mechanisms of immunomodulation by drugs.
Immunomodulators are those extrinsic or intrinsic substances which regulate or alter the scope, type, duration or competency of the immune response. This paper presents an overview of the mechanisms of immunomodulation, and discusses selected chemical and biologic substances which are capable of modifying the immune or biologic response of the organism. The immunopharmacology, including in vivo and in vitro assays, of a novel acridine immunomodulator is discussed. This low molecular weight compound is an immunomodulator and anti-cancer adjuvant, which has been shown to induce high levels of circulating interferon in mice, protect mice against lethal viral infection, stimulate macrophage and NK cell cytotoxicity for tumor cells, partially restore humoral and cellular immune responses in tumor bearing immunosuppressed mice, and augment the cytotoxic T-lymphocyte response to syngeneic tumor cells. Tissue changes, consisting of presence of drug bound to lysosomal membranes, perivascular infiltrates in mouse liver, glomerular hyalinization in mouse kidney, and focal myocardial changes in mice are described. The compound persists intracellularly for extended periods of time in cells with high lysosomal activity. The tissue changes are interpreted to be a result of overloading of cellular mechanisms for elimination from the cells involved.
Lebish
I J
IJ
American Cyanamid Company, Medical Research Division, Wilbur G. Malcolm Toxicology Laboratories, Pearl River, New York 10965.
Moraski
R M
RM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D000276:Adjuvants, Immunologic