Immunological effects of vagus nerve stimulation in murine systemic lupus erythematosus

Date

2018-03-14

Authors

Pham, Grace
Kulp, Dennis
Stauss, Harald
Mathis, Keisa W.

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0000-0002-9048-7048 (Kulp, Dennis)

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Abstract

Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease that principally affects women and is associated with inflammatory pathogenesis of multiple organs. Of the disseminated features of SLE, classical disease processes such as renal injury with hypertension, as well as autonomic nervous system dysregulation, are prevalent. The autonomic dysfunction in SLE is characterized by increased sympathetic activity and concomitant decreased parasympathetic nervous system (PNS) activity; however, it is unknown if impaired PNS activity promotes hypertension and renal injury in SLE. The cholinergic anti-inflammatory pathway (CAP), is an endogenous neuroimmune reflex that regulates cytokine release from immune cells; briefly, the CAP initiates with stimulation of the parasympathetic vagus nerve and culminates in the inhibition of the secretion of pro-inflammatory cytokines from macrophages and other leukocytes. Although it is known that vagal activity is suppressed in SLE, it remains unclear whether this contributes to a diminished CAP promoting inflammation in the disease. We hypothesized that chronic vagus nerve stimulation (VNS) will decrease the inflammatory cascade in SLE through enhancement of the CAP. Methods: Female SLE (NZBWF1) mice (25 weeks of age) were implanted with electrical vagus nerve stimulators that fit the cervical vagus nerve. Only female mice of this well-characterized strain were used, reflecting the prevalence of lupus in women. The mice were then divided into two groups: VNS (n=10) and sham (n=7). Stimulators targeted the vagus nerve continuously for 2 weeks. Results: Spleen weight was slightly increased in SLE/VNS mice compared to SLE/sham mice (0.14 ± 0.03g vs. 0.11 ± 0.01; P=NS). Flow cytometry showed that SLE/VNS mice had slightly less CD3+/CD4+ bone marrow T cells when compared with SLE/sham mice (27.30 ± 9.41% vs. 40.17 ± 7.01%; P=NS). The percentage of mice with albuminuria, an index of renal injury measured by Albustix, was also decreased in SLE/VNS mice compared to SLE/sham mice (10% vs 29%). Conclusions: These results suggest the efficacy of VNS in reducing the inflammatory profile in SLE mice, and that this protection may reduce end-organ disease. Future work will investigate the role of the CAP in quelling inflammation perpetuated by neuroimmune dysregulations in SLE. Studies supported by the American Heart Association (14SDG18320033) and the National Institutes of Health (1K01HL139859)

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Research Appreciation Day Award Winner - 2018 Medical Student Government Association - Best in First Year Class

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