Immunological alterations in murine systemic lupus erythematosus following α7-nicotinic acetylcholine receptor antagonism

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with pathology of multiple organs and the morbidity and mortality that ensues can be reduced with anti-inflammatory strategies. The cholinergic anti-inflammatory pathway, is an endogenous neuroimmune reflex that inhibits pro-inflammatory cytokine release through stimulation of α7 nicotinic acetylcholine receptors (α7nAChR) on splenic immune cells. Our published studies demonstrate anti-inflammatory capability of α7nAChR activation via nicotine, but loss-of-function studies are needed to further delineate the role of this receptor in SLE. Thus, we hypothesized that α7-nicotinic receptor antagonism with methyllycaconitine would exacerbate SLE's inflammatory cascade. Female SLE (NZBWF1) mice were administered methyllylcaconitine (MLA; 10 mg/kg/day IP) or saline for 14 consecutive days starting at 33 weeks of age and were then euthanized with their spleen and bone marrow processed for flow cytometry (n = 4/group). The percentage of splenic CD3+CD8+ T cells was higher in SLE mice treated with MLA (27.9±4.8 vs. 20.4±3.5%; P=NS), but CD3+CD4+ T cells (66.6±4.3 vs. 73.8±3.2%; P=NS) and CD11c dendritic cells (1.9±4.8 vs. 9.2±5.0%; P=NS) were lower in MLA-treated compared to saline-treated SLE mice. CD3+CD8+ T cells were also higher in the bone barrow of MLA-treated SLE (21.3±0.3% vs. 13.9±3.9 %; P=NS). Although not significant, these results suggest blockade of α7nAChRs potentiates the cytotoxic inflammatory profile in SLE mice. Future work will confirm the role of the α7nAChR in potentiating inflammation and end organ damage in SLE.