Immunologic effects of levamisole in mice and humans: evidence for augmented antibody response without modulation of cellular cytotoxicity.
Selected immunomodulatory effects of levamisole were studied in patients with asymptomatic metastatic colon cancer and in a preclinical model (CF1 female mice treated with methyl-azoxymethanol acetate) for colon tumors. In the patient population studied, there was no augmentation of cellular cytotoxicity or alteration in lymphocyte subpopulations that participate in these functions. An increase in Fc receptor binding on circulating monocytes was apparent at the 4-week timepoint; however, a corresponding increase in antibody-dependent cellular cytotoxicity was observed in only one of the six patients studied. In most patients, cellular cytotoxicity diminished with time. No significant effects on cellular immunity or carcinogenesis were observed in our murine studies. However, treatment with levamisole did increase circulating immunoglobulin levels and IgM response in mice immunized with the T-dependent antigen keyhole limpet hemocyanin. This parameter was not tested in the human trial. Failure to demonstrate antitumor effects on cellular immunity by levamisole in both human and murine studies suggests that these effects, if they do exist, may involve immunological parameters that were not tested using our methods or that may not be apparent in patients with more advanced malignancy.
Tempero
M A
MA
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-3330, USA.
Haga
Y
Y
Sivinski
C
C
Birt
D
D
Klassen
L
L
Thiele
G
G
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D007978:Levamisole / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice
D000276:Adjuvants, Immunologic; D007978:Levamisole