Single-dose topical exposure to the pyrethroid insecticide, permethrin in C57BL/6N mice: effects on thymus and spleen

Immunomodulatory effects of single topical exposure to permethrin were evaluated in 5-week-old female C57BL/6N mice. Mice exposed to 5-25 microl permethrin (equivalent to 220-1100 mg/kg body weight) on shaved interscapular skin were evaluated for altered body weight; splenic and thymic organ weight and cellularity; thymocyte cell surface expression, cellular apoptosis; splenic macrophage phagocytosis and hydrogen peroxide production; splenic B cell antibody production and T cell cytolytic activity; and mitogen-induced proliferation of splenocytes and thymocytes after in vivo or in vitro permethrin exposure. Topical permethrin application (25 microl) caused 32% inhibition of splenic T cell proliferation; in vitro exposure to permethrin also diminished splenocyte proliferation by 72% at 25 microM and 86% at 100 microM. permethrin did not appear to affect other leukocyte functional assays. Dose-related decreases in thymic cellularity of 52 and 80% were seen in mice exposed to 15 and 25 microl permethrin, respectively. Apoptosis was significantly increased in CD4(-)8(-) and CD4(-)8(+) thymocytes, and the CD4(+)CD8(+) thymocyte subpopulation was most severely diminished, suggesting possible chemical-induced apoptotic mechanism of thymic atrophy. Permethrin also caused splenic hypocellularity by 31% at 15 microl, and by 50% at 25 microl, an effect that may relate to inhibited proliferation or reduced seeding from the hypocellular thymus.