Aging and sympathetic modulation of immune function in Fischer 344 rats: effects of chemical sympathectomy on primary antibody response

In aged Fischer 344 (F334) rats, sympathetic innervation of the spleen is markedly diminished compared with young rats. To determine if this diminished noradrenergic (NA) innervation maintains a functional connection with the immune system, 3- and 17-month-old male F344 rats were treated with the NA-selective neurotoxin, 6-hydroxydopamine (6-OHDA), to ablate peripheral NA nerve fibers. In sympathectomized rats immunized with keyhole limpet hemocyanin (KLH), a T-dependent protein antigen, anti-KLH IgM, IgG, IgG1, IgG2b antibody titers were increased in young and old rats 14 days after immunization compared to vehicle controls. Furthermore, the number of IgM and IgG anti-KLH antibody-secreting spleen cells was elevated 7 and 14 days post-immunization. These effects were prevented by pretreatment with desipramine, a catecholamine uptake blocker that blocks 6-OHDA uptake and subsequent sympathectomy. Chemical sympathectomy also increased KLH-induced proliferation in vitro by spleen cells from old, but not young animals. Isoproterenol (ISO), a beta-adrenergic receptor agonist, elicited a rise in cAMP in spleen cells from NA-intact young and old rats, but the increase was attenuated in spleen cells from old rats. These results demonstrate that, although NA innervation in the F344 rat spleen is diminished with age, sympathetic signaling of the immune system remains intact. Thus, the SNS can inhibit antibody produced in response to a protein antigen in both young and old F344 rats.