Strain-specific enhancement of splenic T cell mitogenesis and macrophage phagocytosis following peripheral axotomy.

The inbred mouse strains C57BL/6 and DBA/2 were subjected to the selective depletion of peripheral nervous system norepinephrine (NE) by the administration of the neurotoxin 6-hydroxydopamine (6-OH-DA). Measurement of mitogen-induced lymphocyte proliferation following peripheral axotomy with 6-OH-DA revealed that significant enhancement (up to 200% of control values) of T, but not B, cell proliferative responses occurred in DBA/2, while no effect was observed in C57BL/6. Enhancement (up to 196% of control values) of luminol-enhanced chemiluminescence resulting from the phagocytosis of opsonized zymosan was also observed following 6-OH-DA treatment in DBA/2, but not C57BL/6. This strain-specific enhancement of immune responses occurred even though the administration of 6-OH-DA resulted in a similar depletion of splenic NE content (greater than 97% reduction of control values) in both strains as determined by high-pressure liquid chromatography-electrochemical detection. Blockage of the neurotoxic effects of 6-OH-DA was achieved by the use of the catecholamine uptake blocker desipramine-HCl. Administration of desipramine prior to 6-OH-DA blocked the reduction of splenic NE content and abrogated the enhancement of mitogen-induced T cell proliferation. The enhancement of phagocytosis by 6-OH-DA was not, however, altered by the prior administration of desipramine.