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


METHODS
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 < .001) but does not change (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.


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China; Guangzhou Medical College, Guangzhou, China; Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Jinying
J
Yang
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China; Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Shao-Qing
SQ
Shi
Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Leili
L
Shi
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China; Guangzhou Medical College, Guangzhou, China; Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Dajun
D
Fang
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
Huishu
H
Liu
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China; Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ. Electronic address: robert.garfield@chw.edu.
Robert E
RE
Garfield
D000818:Animals; D001724:Birth Weight / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007249:Inflammation / Q000276:immunology*; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000276:immunology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists
D015850:Interleukin-6; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D016753:Interleukin-10; D009538:Nicotine
cytokines; inflammation; nicotine; parturition; preeclampsia; preterm birth; α7 nicotinic acetylcholine receptor agonist