The Influence of Single or Repeated Low‐Level Sarin Exposure on Immune Functions of Inbred BALB/c Mice

Abstract

To study the influence of single or repeated low-level sarin inhalation exposure on immune functions, inbred BALB/c mice were exposed to low clinically asymptomatic concentrations of sarin for 60 min. in the inhalation chamber. The evaluation of immune functions was carried out using phenotyping of CD3 (T-lymphocytes), CD4 (helper T-lymphocytes), CD8 (cytotoxic T-lymphocytes) and CD19 (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 one week after sarin exposure. The results were compared to the values obtained from control mice exposed to pure air instead of sarin. The results indicate that an asymptomatic dose of sarin is able to alter the reaction of the immune system at one week after exposure to sarin. While the number of CD3 cells in lung was significantly decreased, a slight increase in CD19 cells was observed especially in the lungs after a single sarin inhalation exposure. Lymphoproliferation was significantly decreased regardless of the mitogen and sarin concentration used and the number of low-level sarin exposures. The ability of peritoneal and alveolar macrophages to phagocyte the microbes was also decreased regardless of the number of low-level sarin exposures. The production of N-oxides by peritoneal macrophages was decreased following a single low-level sarin exposure but increased following repeated low-level sarin inhalation exposure. Nevertheless, the changes in the production of N-oxides that reflects a bactericidal activity of peritoneal macrophages was not significant. The natural killer cell activity was significantly higher in the case of inhalation exposure of mice to low concentration of sarin regardless of the number of exposures. Thus, not only organophosphorous insecticides but also nerve agents such as sarin are able to alter immune functions following a single inhalation exposure even at a dose that does not cause clinically manifested intoxication. Generally, the repeated exposure to low concentrations of sarin does not increase the alteration of immune functions compared to the single low-level sarin exposure with the exception of phagocyte activity of alveolar macrophages and natural killer cell activity.