ALTERATIONS IN CYTOKINE AND ANTIBODY-PRODUCTION FOLLOWING CHEMICAL SYMPATHECTOMY IN 2 STRAINS OF MICE

It is becoming clear that immune responses are subject to modulation b y the sympathetic nervous system. We examined the effect of chemical s ympathectomy (to ablate peripheral sympathetic nerve fibers) on cytoki ne and Ab production in two strains of mice that are known to differ i n their response to a variety of pathogens and in the dominant types o f cytokines produced. C57Bl/6J mice produce a strong cell-mediated res ponse, characterized by production of IL-2 and IFN-gamma, whereas BALB /cJ have a dominant humoral response, with production of IL-4 and IL-1 0. Animals were denervated by injection with 6-hydroxydopamine and imm unized with keyhole limpet hemocyanin, and spleens were removed at var ious times after immunization. Denervation significantly increased the keyhole-limpet-hemocyanin-stimulated in vitro proliferation and IL-2 and IL-4 production by splenocytes from both strains. The increases we re prevented by pretreatment with desipramine, which blocks the uptake of 6-hydroxydopamine into the nerve fibers and subsequent nerve fiber destruction. Serum titers of IgM, IgG, IgG1, and IgG(2a) were also en hanced in the C57Bl/6J strain; BALB/cJ mice had a small increase in Ig G1 only. These results suggest that one function of splenic innervatio n and transmitter release may be to modulate T helper cytokines, there by partially regulating immune effector function. Our evidence is cons istent with a model of immune regulation in which removal of sympathet ic nervous system input enhances at least some parameters of immune re sponses.