Abstract # 1824 Healthy smokers’ peripheral blood lymphocytes exhibit differential inflammatory gene expression to glucocorticoid and lipopolysaccharide exposure

Cigarette smoking is linked to elevated inflammation and development of chronic inflammation-related conditions such as asthma, autoimmune diseases, and chronic bronchitis. Among these patient populations, those who smoke often have poorer symptom management/relief via usual treatments, including glucocorticoids, suggesting glucocorticoid resistance. Even less is understood about the early changes in smokers’ immune function especially those who have not yet developed a clinical disease. Thus, we recruited healthy smokers (e.g., no clinical diagnoses or current medication use) and age-, sex-, and BMI-matched never smokers to examine glucocorticoid sensitivity. Following a 12-h fast, 47 adults (30.5 +/−8.1 yrs; 27 males) provided a blood sample and answered several psychosocial questionnaires. Using a repeated-measures ANOVA, dexamethasone significantly reduced all peripheral blood lymphocytes’ (PBLs) IL-6, TNF-alpha, and IFN-gamma mRNA expression response to lipopolysaccharide (LPS; p < .05). In addition, dexamethasone‘s immunosuppressive effect was significantly greater in never smokers for TNF-alpha and IFN-gamma mRNA expression ( p < .05) and trended for IL-6 ( p = .07) compared to smokers. Thus, our data suggest that even prior to chronic disease development and elevated systemic inflammation (i.e., CRP levels < 0.25 mg/L), PBLs show diminished activation to LPS, indicating that immune system dysregulation occurs long before clinical symptoms develop and may be linked to glucocorticoid resistance. These provocative data necessitate additional research into the underlying intracellular changes as well as may lead to novel targets to minimize these negative immune adaptations.