The sympathetic nervous system can signal cells of the immune system through release of
norepinephrine (NE), and may thus modulate several aspects of immune reactivity. We have examined the consequences of chemical
denervation using
6-hydroxydopamine (6-OHDA) on the response of BALB/c mice to
tumor cell challenge. In this study, chemical
axotomy prior to the intravenous (i.v.) injection of the
alveolar carcinoma line 1 significantly increased the number of pulmonary
metastases. In contrast,
axotomy performed after i.v. injection of
tumor cells had no effect on the number of lung
metastases. Line 1
tumor cells have been reported to be susceptible to lysis by natural killer (NK) cells. To examine possible mechanisms through which prior
axotomy leads to increased lung
metastases, we tested the effects of
axotomy on in vitro and in vivo NK cell activity. No differences in NK cell activity were found between 6-OHDA- and vehicle-treated mice. Line 1
tumor cell growth in vitro was unaffected by both
6-OHDA and NE, and the
tumor cells do not express
beta-adrenergic receptors. Priming mice with lethally irradiated line 1 cells significantly reduced the number of lung
metastases following challenge with live
tumor cells;
axotomy did not alter this decrease in
metastases associated with priming. In summary, chemical
axotomy of mice prior to injection of
alveolar carcinoma cells resulted in an increased number of pulmonary
metastases that was not correlated with alterations in either NK cell cytotoxicity or the putative immunological consequences of in vivo priming.