Influence of heavy metals on the resistance of mice toward infection.

Previous studies have shown that heavy metals may exert marked immunomodulatory effects, at least in rodents, despite some discrepancies. However, the mechanism of their influence on the immune system is still unclear. As host resistance assays against experimental infections are generally considered as the most relevant criteria when predicting the immunotoxicity of drugs and chemicals, the effects of lead acetate, nickel chloride and sodium selenite on the resistance toward experimental Klebsiella pneumoniae infection was investigated in mice, with particular emphasis on the interference of the time of toxic exposure with the infectious challenge. Interestingly, one single intraperitoneal dose of 24 mg/kg lead or 4 mg/kg nickel enhanced the resistance of mice against Klebsiella pneumoniae when administered 24 hours before the infectious challenge, whereas host resistance proved to be impaired when the same dose was injected 5 hours after the infectious challenge. A 3-day pretreatment with 8 or 12 mg/kg lead also enhanced the resistance of mice but decreased it with 0.5 or 1 mg/kg nickel. In all cases, sodium selenite increased the resistance of mice toward infection. As lead, nickel and selenium appear to exert complex and possibly opposite effects on antibody response and phagocytosis, it remains to establish which immunotoxic consequences if any, an acute or chronic exposure to these heavy metals is likely to have in man.