Int J Biol Sci 2018; 14(7):748-759. doi:10.7150/ijbs.24576
Activation of Central Alpha 7 Nicotinic Acetylcholine Receptor Reverses Suppressed Immune Function of T Lymphocytes and Protects Against Sepsis Lethality
1. Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, People's Republic of China.
2. School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
3. Emergency Department, Jin Hua Municipal Central Hospital, Jinhua 321001, People's Republic of China.
4. State Key Laboratory of Kidney Disease, the Chinese PLA General Hospital, Beijing 100853, People's Republic of China.
Chao Ren, Xiu-hua Li, and Shi-bin Wang have contributed equally to this work.
Sepsis remains the leading cause of high mortality and huge financial burden in intensive care units (ICU), but with scarce effective treatments due to refractory multiple organ dysfunction and persistent immunosuppression. Treatments that aim at modulating immune function and attenuating multiple organ injury will certainly benefit septic cases. Alpha 7 nicotinic acetylcholine receptor (α7nAchR) has been reported with potent immunomodulatory properties in various diseases as the essential mediator of the cholinergic anti-inflammatory pathway (CAP). Few studies have demonstrated the potential effect of central α7nAchR on the progression and prognosis of septic response, while its expression was first discovered on neurons and most abundant in the central nervous system. In the present study, it was found severe damage of multiple organs under the operation of cecal ligation and puncture (CLP) in rats, including heart, liver, kidneys, and lungs, as evidenced by abnormal histomorphology and notable elevation of injury markers. Concurrently, the function of spleen CD4+ T cells was disrupted under septic challenge, accompanied by polarization of helper T cell (Th)2, which exhibited outward signs of immunosuppression. Intracerebroventricular injection of PNU282987, a selective agonist of α7nAchR, significantly alleviated multiple organ injury, reversed immunosuppressive state, and improved the outcome of septic rats, while they were exacerbated by treatment with methyllycaconitine, a selective antagonist of α7nAchR. This study provides the first evidence that activation of central α7nAchR is beneficial for attenuating multiple organ dysfunction as well as abnormal immune response, and improving the prognosis of rats when exposed with sepsis.
Keywords: Alpha 7 nicotinic acetylcholine receptor, sepsis, immune response, multiple organ dysfunction syndrome, prognosis
Ren C, Li Xh, Wang Sb, Wang Lx, Dong N, Wu Y, Yao Ym. Activation of Central Alpha 7 Nicotinic Acetylcholine Receptor Reverses Suppressed Immune Function of T Lymphocytes and Protects Against Sepsis Lethality. Int J Biol Sci 2018; 14(7):748-759. doi:10.7150/ijbs.24576. Available from http://www.ijbs.com/v14p0748.htm