The role of parity status on cigarette smoke-induced modulation of anti-tumor immune mechanisms

Abstract

Epidemiologic studies indicate that women who smoke cigarettes are more likely to experience adverse reproductive and immunological health effects. Despite these facts, 20–30% of American women still smoke during their reproductive years. As little is known of the relationship between smoking and the immune response during pregnancy, an investigation was conducted using parous and non-parous (virgin) B6C3F1 mice to investigate what role (if any) parity status had on cigarette smoke (CS) induced effects on immune functions important in surveillance against developing tumors. Pregnant mice were exposed to CS for 5 d/wk ( 4 hr/d) from gestational day 4 to parturition; virgin mice were exposed for an equivalent amount of time. Smoke- and parity-associated alterations in pulmonary histology and lung inflammation, along with tumor cell host resistance, and cytotoxic T-lymphocyte (CTL) activity were examined either 24- 48 hr or 5 wk post-exposure/parturition; in the parous mice, gestational parameters were also evaluated. Exposure to CS significantly increased tumor susceptibility in virgin mice first injected with EL4 lymphoma cells at the 5 wk post-exposure timepoint; tumor incidence began to increase in smoke-exposed virgin mice as early as 24– 48 hr post-exposure. Pregnancy itself increased tumor incidence in mice injected with EL4 cells 24– 48 hr after birth, but this effect then dissipated over 5 wk to levels seen in virgin mice. When EL4 injections were first performed at either timepoint in CS-exposed parous mice, the tumor incidence was not significantly different from that in the air-exposed parity-matched controls. CTL activity in CS-exposed parous mice was significantly increased from both nulliparous groups as well as from the parous air control mice examined 5 wk post-exposure. Results suggest that exposure to CS throughout gestation could act in combination with pregnancy-associated changes to up-regulate immune responses, potentially compromising fetal tolerance.

Keywords::

• Cigarette smoke
• immunomodulation
• parity status
• tumor surveillance

Acknowledgments

This research was supported by Philip Morris USA Inc. and Philip Morris International, and (in part) by New York University (NYU) National Institute of Environmental Health Sciences (NIEHS) Center Grant (ES00260). The authors would like to thank Shannon Doherty, Carol Hoffman, and Sally Lasano for their technical assistance, Dr. Maarten Bosland for some histological analyses, and Dr. Bernard Steinetz for his valuable input on gestational measurements.

Declaration of interest: None of the authors has any conflicts of interest to disclose. The authors alone are responsible for the content and writing of the paper.