The Effects of Prenatal Exposure of Mice to Cigarette Smoke on Offspring Immune Parameters

Abstract

While direct exposure to cigarette smoke (CS) was shown in numerous human and animal studies to impair host immune responses, effects on the offspring following in utero CS exposure are relatively unknown. Thus, a toxicological study was performed that extended our previous investigations examining the effects of relatively low-dose CS exposure on immune tumor surveillance parameters of the prenatally exposed offspring. In the current study, pregnant B6C3F1 mice were exposed by inhalation to mainstream CS (at a concentration equivalent to smoking ∼1 pack of cigarettes/d) for 5 d/wk, 4 h/d from gestational day 4 to parturition. Smoke-induced effects on a number of immune parameters were examined in 3- (and/or 5-), 10-, and 20-wk-old male and female offspring, including lymphoid organ weight/cellularity; blood and bronchopulmonary lavage cell numbers/profiles; splenic lymphocyte proliferation; mixed lymphocyte reactions; and, host resistance against transplanted melanoma cells. Exposure in utero to CS significantly increased circulating white blood cell and lymphocyte numbers in both sexes for up to 2.5 mo after birth (compared to their age-/sex-matched, air-exposed counterparts). In addition, 3-wk-old male and female offspring from smoke-exposed mothers had decreased mitogen-stimulated T-lymphocyte proliferation, while 5-wk-old male pups had increased mixed lymphocyte response compared to their sex-matched, air-exposed counterparts. Although effects of prenatal smoke exposure on overall offspring immunity were relatively modest, these findings could suggest that early toxic insult by CS may alter subsequent immune homeostasis in the offspring, leading, possibly, to changes in disease vulnerability.

This study received funding from Philip Morris USA, Inc., and Philip Morris International, and the New York University National Institute of Environmental Health Sciences, center grant ES00260. The authors thank Shannon Doherty-Lyons and Maureen Sisco for their technical assistance.