|Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
The crosstalk between immune system and nerve system is known to be involved in homeostasis. We studied the crosstalk betwwen these to systems in Listeria monocytogenes (LM)-infected mouse model from the standpoints of the interactions between neuropeptides, sympathetic nerve system, host defense, and cytokine production.
1 We investigated the effects of neuropeptides such as substance P (SP) and vasoactive intestinal peptide (VIP) on IFN-gamma and TNF-alpha production induced by heat-killed LM (HK-LM) in spleen cell cultures obtained from naive mice and LM-immunized mice. Neither neuropeptides affected the productions these cytokines. Next, to know the autocrine and paracrine actions of neuropeptides, antibodies against SP and VIP were added the cultures. Neither antibodies affected on the productions of IFN-gamma and TNF-alpha.
2 We investigated the effects of in vivo administration of alpha-melanocyte-stimulating hormone (alpha-MSH) on LM infection and cytokine production. No signific
ant effect of alpha-MSH on antilisterial defense and the productions of IFN-gamma and TNF-alpha induced by HK-LM in spleen cell cultures.
3 When mice was pretreated with 6-hydroxydopamine (6-OHDA), which destroys noradrenergic nerve terminals, host defense to LM was augmented late in infection. This effect was prevented by pretreatment with desipramine, which blocks the uptake of 6-OHDA into the nerve fibers.
4 We inverstigated the effects of denervation by 6-OHDA on endogenous IFN-gamma, TNF-alpha, and IL-12 production induced by infection with LM in the spleens of mice. No effect of denervation on endogenous cytokine production was observed. However, TNF-alpha production induced by HK-LM and IFN-gamma production induced by anti-CD3 mAb was enhanced in spleen cell cultures obtained from 6-OHDA-pretreated mice.
Our results demonstrated that host defense to LM infections and the productions of IFN-gamma, and TNF-alpha, which are crucial in the defense, were augmented by block of the sympatheic nerve system, suggesting that host defense to LM infection might be depend on the interactions between immune system and nerve system. Less