Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection

Troy J. Kemp, Allan Hildesheim, Alfonso García-Piñeres, Marcus C. Williams, Gene M. Shearer, Ana Cecilia Rodriguez, Mark Schiffman, Robert D. Burk, Enrique Freer, Jose Bonilla, Rolando Herrero, Ligia A. Pinto

Research output: Contribution to journalArticle

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Abstract

Background: Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have 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 (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for 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 < 0.0001); and IL-1α, 218.2 versus 169.5 (P = 0.02).We focused our analysis on the cytokines IL-6, IL-8, TNF-α, and MIP-1α due to their high fold change (>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 infection in 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.

Original languageEnglish (US)
Pages (from-to)1954-1959
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number8
DOIs
StatePublished - Aug 2010

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Papillomavirus Infections
Cytokines
Macrophage Inflammatory Proteins
Blood Cells
Cell Culture Techniques
Interleukin-1
Interleukin-6
Tumor Necrosis Factor-alpha
Phytohemagglutinins
Granulocyte-Macrophage Colony-Stimulating Factor
Infection
Interleukin-8
Mitogens
Immunoassay
Uterine Cervical Neoplasms
Enzyme-Linked Immunosorbent Assay
Antigens

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Kemp, T. J., Hildesheim, A., García-Piñeres, A., Williams, M. C., Shearer, G. M., Rodriguez, A. C., ... Pinto, L. A. (2010). Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection. Cancer Epidemiology Biomarkers and Prevention, 19(8), 1954-1959. https://doi.org/10.1158/1055-9965.EPI-10-0184

Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection. / Kemp, Troy J.; Hildesheim, Allan; García-Piñeres, Alfonso; Williams, Marcus C.; Shearer, Gene M.; Rodriguez, Ana Cecilia; Schiffman, Mark; Burk, Robert D.; Freer, Enrique; Bonilla, Jose; Herrero, Rolando; Pinto, Ligia A.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 19, No. 8, 08.2010, p. 1954-1959.

Research output: Contribution to journalArticle

Kemp, TJ, Hildesheim, A, García-Piñeres, A, Williams, MC, Shearer, GM, Rodriguez, AC, Schiffman, M, Burk, RD, Freer, E, Bonilla, J, Herrero, R & Pinto, LA 2010, 'Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection', Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 8, pp. 1954-1959. https://doi.org/10.1158/1055-9965.EPI-10-0184
Kemp, Troy J. ; Hildesheim, Allan ; García-Piñeres, Alfonso ; Williams, Marcus C. ; Shearer, Gene M. ; Rodriguez, Ana Cecilia ; Schiffman, Mark ; Burk, Robert D. ; Freer, Enrique ; Bonilla, Jose ; Herrero, Rolando ; Pinto, Ligia A. / Elevated systemic levels of inflammatory cytokines in older women with persistent cervical human papillomavirus infection. In: Cancer Epidemiology Biomarkers and Prevention. 2010 ; Vol. 19, No. 8. pp. 1954-1959.
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abstract = "Background: Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have 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 (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for 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 < 0.0001); and IL-1α, 218.2 versus 169.5 (P = 0.02).We focused our analysis on the cytokines IL-6, IL-8, TNF-α, and MIP-1α due to their high fold change (>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 infection in 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.",
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AU - García-Piñeres, Alfonso

AU - Williams, Marcus C.

AU - Shearer, Gene M.

AU - Rodriguez, Ana Cecilia

AU - Schiffman, Mark

AU - Burk, Robert D.

AU - Freer, Enrique

AU - Bonilla, Jose

AU - Herrero, Rolando

AU - Pinto, Ligia A.

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N2 - Background: Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have 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 (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for 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 < 0.0001); and IL-1α, 218.2 versus 169.5 (P = 0.02).We focused our analysis on the cytokines IL-6, IL-8, TNF-α, and MIP-1α due to their high fold change (>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 infection in 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.

AB - Background: Defects in lymphoproliferative responses to mitogens/antigens in women >45 years old with a persistent type-specific human papillomavirus (HPV) infection have 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 (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for 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 < 0.0001); and IL-1α, 218.2 versus 169.5 (P = 0.02).We focused our analysis on the cytokines IL-6, IL-8, TNF-α, and MIP-1α due to their high fold change (>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 infection in 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.

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