Nicotine, an α7 nAChR agonist, reduces lipopolysaccharide-induced inflammatory responses and protects fetuses in pregnant rats

• Published in: American journal of obstetrics and gynecology 2014-11, Vol.211 (5), p.538.e1-538.e7
• Main Authors: Yang, Jinying, MD, Shi, Shao-Qing, MD, Shi, Leili, DDS, Fang, Dajun, MD, Liu, Huishu, MD, PhD, Garfield, Robert E., PhD
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor - agonists; Animals; Birth Weight - drug effects; cytokines; Female; Fetus - drug effects; inflammation; Inflammation - immunology; Injections, Intraperitoneal; Interleukin-10 - immunology; Interleukin-6 - immunology; Lipopolysaccharides - pharmacology; nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Obstetrics and Gynecology; parturition; preeclampsia; Pregnancy; Pregnancy Outcome; preterm birth; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - immunology; α7 nicotinic acetylcholine receptor agonist
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2014.04.026

Objective The objective of the study was to examine the effects of nicotine, an α7 nicotinic acetylcholine receptor agonist, on lipopolysaccharide (LPS)-induced inflammatory responses in rats during pregnancy. Study Design Pregnant Sprague Dawley rats were randomly divided into groups (n = 6 rats/group): group 1 rats each received a single intraperitoneal injection of LPS (25 μg/kg) on gestation day 16; group 2 rats were first pretreated with nicotine (1 mg/kg per day, subcutaneously) on gestation days 14 and 15 and then were treated with single injections of LPS on gestational day 16; group 3 rats were treated with the vehicle (saline) used for groups 2 and 3 (controls). Maternal blood was collected at 6 hours and 24 hours after LPS and vehicle treatments and assayed for tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-10 (IL-10). In addition, the number of live pups and pup weights were obtained at the time of delivery. Results LPS treatment significantly ( P < .001) elevates maternal blood levels of TNF-α and IL-6 but not IL-10 ( P > .05). Nicotine treatment significantly reduces LPS-induced TNF-α and IL-6 concentrations ( P   .05) IL-10 levels. The number of live pups in the LPS group are significantly lower ( P < .001) than the vehicle treated controls, and nicotine treatment significantly ( P < .011) reverses this change. Similarly, fetal weights are lower following LPS ( P < .016) and higher ( P < .024) in the group treated with nicotine plus LPS. Conclusion Nicotine reduces the LPS-induced inflammatory responses and rescues the fetus in rats during pregnancy. Thus, nicotine exerts dramatic antiinflammatory effects. These observations have important implications for control of inflammatory responses during pregnancy.