Contrasting pattern of cytokines in antigen- versus mitogen-stimulated splenocyte cultures from chemically denervated mice.

Sympathetic nervous system (SNS) regulation of immune function has been studied by ablating the SNS with a peripheral injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Our previous data indicate that sympathectomy of mice results in enhanced antibody production and in vitro levels of antigen-specific IL-2 and IFN-gamma. Other investigators have observed either increased or decreased immune function following sympathectomy. Here we present data showing that culture supernatants from spleen cells from the same denervated animals contain increased IL-2 and IFN-gamma levels in response to antigen-specific (keyhole limpet hemocyanin (KLH)) stimulation, but decreased cytokines levels in response to the T cell mitogen Con A compared to vehicle control mice. KLH-induced type 2 cytokines were also increased; no decrease in Con A-stimulated type 2 cytokines was observed. We evaluated whether the antigen presenting cell (APC) or the T cell might be the main target of the observed sympathectomy effects. Cell separation and mixing experiments suggest that the sympathectomy-induced alterations of antigen-specific and mitogen-induced type 1 cytokines are mediated primarily via the T cell. These data directly address some apparent discrepancies in the literature, and highlight potential regulatory sites to be further investigated in pathways of neural-immune communication.