Enhancement of natural killer cell activity and interferon production by manganese in young mice

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 40 micrograms 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 alpha, beta but not gamma completely abrogated the enhanced NK activity. In addition, the injection of rabbit anti-mouse interferon alpha, beta but not gamma 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 alpha, beta.