Enhancement of Natural Killer Cell Activity and Interferon Production by Manganese in Young Mice

Abstract

The effect that MnCl₂ has on murine splenic natural killer (NK) cell activity was investigated in infant (10 days old), pre-weanling (18 days old) and weanling (24 days old) C57BL/6J mice. A single intraperitoneal injection of 10, 20 or 40μg MnCl₂/g body weight caused a significant enhancement in NK activity, as determined by the in vitro ⁵¹Cr release assay. Comparable enhancement of NK activity was observed for age-matched mice injected intraperitoneally with polyinosinic polycytidylic acid (Poly I:C). Both MnCl₂ and Poly I:C caused elevations in serum interferon levels. Time-course studies revealed that interferon levels returned to normal within 48 hours following injection with either MnCl₂ or Poly I:C; however enhanced NK activity persisted for up to 48 hours in Poly I:C-injected mice and 72 hours in MnCl₂-injected mice. The administration of rabbit anti-asialo GMl to MnCl₂-injected mice completely abrogated the enhanced NK activity. In addition, the injection of rabbit anti-mouse interferon a, α, β but not γ completely abrogated the enhancement of NK activity by MnCl₂ and to a lesser extent the enhancement of NK activity by Poly I:C. These results indicate that despite low levels of NK activity in pre-weanling mice, MnCl₂ is capable of enhancing this activity by 8–9 fold. Furthermore, Mn-enhanced NK activity in these young mice appears to be mediated by the production of interferon α, β.