Elevated Systemic Levels of Inflammatory Cytokines in Older Women with Persistent Cervical Human Papillomavirus Infection

Background: Defects in lymphoproliferative responsesto mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus ( HPV) infectionhave been reported. Methods: To determine whether these defects were associated with altered cytokine profiles, plasma and peripheral blood mononuclear cell (PBMC) culture supernatants from 50 cases ( oversampledfor their reduced lymphoproliferative ability) and 50 uninfected controls ( oversampledfor their robust lymphoproliferative ability) were examined for 24 cytokines using multiplexed bead–based immunoassays and ELISA. Results: The following plasma cytokines were significantly increased in cases relative to controls (cases versus controls; median pg/mL): interleukin (IL)-6, 393.1 versus 14.5; IL-8, 1,128.5 versus 43.9; tumor necrosis factor-α (TNF-α), 164.1 versus 9.2; macrophage inflammatory protein-1α (MIP-1α), 1,368.9 versus 25.5; granulocyte macrophage colony-stimulating factor(GM-CSF), 13.8 versus 7.3; IL-1β, 8.3 versus 1.6 (all P 10) and highly statistically significant difference between cases and controls. Length of persistence or type of infection (high risk and low risk) did not affect these differences. IL-6, TNF-α, and MIP-1α levels were also increased in unstimulated PBMC culture supernatants from cases compared with controls ( P < 0.05), however, the cytokine levels from phytohemagglutinin-stimulated PBMC culture supernatants were significantly lower in the cases ( P < 0.0001). Conclusions: Persistent HPV infectionin older women with evidence of immune deficit is associated with an increase in systemic inflammatory cytokines. Impact: Future studies are needed to determine whether the inflammatory profile is age dependent and to examine the role that inflammatory cytokines play in HPV-induced progression from infection to cervical cancer. Cancer Epidemiol Biomarkers Prev; 19(8); 1954–9. ©2010 AACR.