Enhancement of in vitro lipopolysaccharide-stimulated interleukin-1 production by levamisole.
The production of interleukin-1 (IL-1) by the P388D1 mouse macrophage cell line and by adherent peritoneal exudate cells (PMs) was examined. In vitro IL-1 production by P388D1 cells treated with lipopolysaccharide (LPS) was enhanced by coculture with levamisole (0.1 to 10 microM). Oral administration of levamisole (3 mg/kg) to mice also resulted in potentiation of in vitro IL-1 production by thioglycollate-elicited peritoneal macrophages in response to in vitro LPS stimulation. Potentiation was approximately twofold. IL-1 production in the absence of LPS by either the P388D1 cells or the PMs was nil, and levamisole did not directly stimulate IL-1 production in these cases. IL-1 activity in the culture supernatants was measured by thymocyte comitogenic assays. The immunochemical identify of the thymocyte comitogenic activity as IL-1 alpha was confirmed by neutralization with a specific goat anti-mouse IL-1 alpha antiserum. These results suggest that one mechanism by which levamisole acts to normalize and restore immune responses may be enhancing the signals which enable activated macrophages to secrete IL-1.
Kimball
E S
ES
Department of Biological Research, Janssen Research Foundation, Spring House, Pennsylvania 19477.
Clark
M C
MC
Schneider
C R
CR
Persico
F J
FJ
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D007978:Levamisole / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000502:physiology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011233:Precipitin Tests; D014176:Protein Biosynthesis / Q000187:drug effects
D007093:Imidazoles; D048289:Imidazolidines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D007978:Levamisole; C019204:OMPI