Effects of early exposure to environmental tobacco smoke on the systemic and pulmonary immune system in infant monkeys

Background. Environmental tobacco smoke (ETS) is a common indoor air pollutant. Epidemiological studies have shown that children's exposure to ETS during fetal development and early postnatal life is associated with an increased incidence of allergic and infectious diseases among children. It has been speculated that the immaturity of the neonatal immune system may play a role in the observed associations of ETS exposure in infants and children. Objective. To investigate the effects of ETS exposure on the systemic and pulmonary immune system during the first year of life in the nonhuman primate. Methods. Fifteen neonatal rhesus monkeys studied to 13 months postnatal age were randomized into three groups: (1) filtered air (FA); (2) continuous ETS exposure beginning at gestation day 50 (perinatal ETS) and (3) exposure to ETS beginning at 6 months of age (postnatal ETS). Complete blood counts, lymphocyte subsets and mRNA levels of 12 cytokines in peripheral blood mononuclear cells (PBMCs) were measured in the peripheral blood. mRNA or protein expression of various Th1 and Th2 cytokine, chemokine and chemokine receptors as well as transcription factors were measured in the lung tissue. Results. In the peripheral blood, two weeks' subacute exposure to ETS in postnatal ETS group significantly increased levels of peripheral blood neutrophils and IL-6 mRNA. Fetal/infant exposure to ETS altered the normal maturation of mRNA levels of IFN-gamma, IL-2, IL-10 as well as the ratio of CD4 to CDS lymphocytes, compared to FA controls. Blood lymphocyte subset distribution also significantly differed, based on the onset of exposure to ETS. In the lung tissue, both perinatal and postnatal exposure to ETS had fewer CXCR3 positive immune cells and decreased expression of IFN-gamma and IL-12 in the lungs compared to FA. The mRNA expression of IFN-gamma inducible chemokines IP-10, MIG, ITAC, chemokine receptor CXCR3 and type 2 related chemokine TARC as well as transcription factor t-bet significantly differ between perinatal ETS and FA controls. Conclusions. Perinatal/postnatal exposure to ETS impaired normal Th1 immune maturation in the peripheral blood and the lung. Blood profiling can serve as an early indicator of ETS effects on the developing immune system.