Conditioned medium from activated splenocytes increases substance P in sympathetic ganglia

Following removal of the presynaptic input to the superior cervical ganglion (SCG) of the neonatal rat, there is an increase in substance P (Kessler et al.: Science 214:335-336, 1981; Kessler and Black: Brain Res 234:182-187, 1982) and the mRNA coding for its prohormone precursor (Roach et al.: Proc Natl Acad Sci USA 84:5078-5081, 1987). However, the functional significance of this increase has been unclear. We report here that SP increases dramatically in cultures of SCG grown in the presence of conditioned medium from con-A-stimulated splenocytes. The effect is mimicked by growing SCG explants in the presence of human recombinant interleukin-1 (hrIL-1) but not hrIL-2. Nerve growth factor (NGF) is not involved in mediating this effect since antibodies to NGF included in the culture fail to alter the lymphokine-induced increase in SP. Moreover, the effect is somewhat specific for SP since the activities of tyrosine hydroxylase, tryptophan hydroxylase, and choline acetyltransferase (enzymes in the biosynthetic pathways for norepinephrine, serotonin, and acetylcholine) are not similarly elevated. Dorsal root ganglia respond with only modest increases in SP. The action of lymphokines in stimulating SP may, therefore, be a ganglion-specific action in promoting recovery following injury.