NERVE GROWTH-FACTOR AND CYTOKINES MEDIATE LYMPHOID TISSUE-INDUCED NEURITE OUTGROWTH FROM MOUSE SUPERIOR CERVICAL-GANGLIA IN-VITRO

Superior cervical ganglia (SCG) from neonatal mice were cultured with adult murine lymphoid tissue explants in Matrigel (Collaborative Biome dical, Bedford, MA). After 1 and 2 days in culture, many neurites grew toward thymus and spleen. Normal mesenteric lymph node (MLN) induced a smaller effect; however, activated MLN (isolated from mice 10 days a fter infection with Nippostrongylus brasiliensis; Nb-MLN-10d) caused s ignificantly increased neurite outgrowth. To determine the roles of ne rve growth factor (NGF) and cytokines in the promotion of neuritogenes is by lymphoid tissues, anti-NGF and various anti-cytokines were added to cocultures. Anti-NGF inhibited most of the neurite outgrowth towar d thymus and spleen but only partially that toward Nb-MLN-10d. Anti-mo use IL-1 beta also significantly reduced the number of neurites growin g toward thymus, spleen, and normal MLN; The number of neurites growin g toward Nb-MLN-10d was significantly reduced by anti-IL-1 beta, anti- IL-3, anti-IL-6, or anti-GM-CSF. Exogenous IL-1 beta and IL-3 caused n eurite outgrowth in single SCG cultures; and the IL-1 beta-, but not t he IL-3-, mediated effect was completely blocked by anti-NGF. In one-d ay thymus/SCG cocultures, endogenous IL-1 was not detectable at concen trations sufficient to cause nerve growth; however, ample NGF was pres ent in the thymic tissues and culture supernatants, but not in SCG. Th ese data suggest that IL-1 mediates NGF production in lymphoid tissues , which in turn induces the growth of sympathetic nerves. Moreover, IL -3, IL-6, or GM-CSF produced during inflammation might also play impor tant roles in the stimulation of nerve growth in vivo.