Low-level sarin-induced alteration of immune system reaction in inbred BALB/c mice.
To study the influence of low-level sarin inhalation exposure on immune functions, inbred BALB/c mice were exposed to low concentrations of sarin for 60 min in the inhalation chamber. Two concentrations of sarin were chosen-asymptomatic concentration (LEVEL 1) and non-convulsive symptomatic concentration (LEVEL 2). The evaluation of immune functions was carried out using phenotyping of CD3 (T-lymphocytes), CD4 (helper T-lymphocytes), CD8 (cytotoxic T-lymphocytes) and CD19 cells (B-lymphocytes) in the lungs, blood and spleen, lymphoproliferation of spleen cells stimulated in vitro by various mitogens (concanavalin A, lipopolysaccharides), phagocyte activity of peritoneal and alveolar macrophages, production of N-oxides by peritoneal macrophages and the measurement of the natural killer cell activity at 1 week following sarin exposure. The results were compared to the values obtained from control mice exposed to pure air instead of sarin. The results indicate that not only symptomatic but also asymptomatic dose of sarin is able to alter the reaction of immune system at 1 week following exposure to sarin. While the number of CD3 cells in the lungs was slightly decreased, an increase in CD19 cells was observed especially in the lungs and blood. The reduced proportion of T-lymphocytes is caused by decay of CD4 positive T-cells. Lymphoproliferation was significantly decreased regardless of the mitogen and sarin concentration used. The production of N-oxides by peritoneal macrophages was stimulated after exposure to LEVEL 2 of sarin whereas their ability to phagocyte the microbes was increased after exposure to LEVEL 1. The natural killer cell activity was significantly higher in the case of inhalation exposure of mice to LEVEL 2 of sarin. Thus, not only organophosphorus insecticides but also nerve agents such as sarin are able to alter immune functions even at a dose that does not cause clinically manifested intoxication following the inhalation exposure. Nevertheless, the alteration of immune functions following the inhalation exposure to a symptomatic concentration of sarin seems to be more pronounced.
Kassa
Jirí
J
Department of Toxicology, Purkyne Military Medical Academy, P.O. Box 35/T, 500 01 Hradec Králové, Czech Republic. kassa@pmfhk.cz
Krocová
Z
Z
Sevelová
L
L
Sheshko
V
V
Kasalová
I
I
Neubauerová
V
V
D000280:Administration, Inhalation; D000818:Animals; D018941:Antigens, CD19 / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology; D015704:CD4 Antigens / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis; D012524:Sarin / Q000008:administration & dosage / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000378:metabolism
D018941:Antigens, CD19; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D002619:Chemical Warfare Agents; D008070:Lipopolysaccharides; D008934:Mitogens; D003208:Concanavalin A; D009569:Nitric Oxide; D012524:Sarin