Increased secretion patterns of interleukin-10 and tumor necrosis factor-alpha in cervical squamous intraepithelial lesions

• Published in: Human pathology 2004-11, Vol.35 (11), p.1376-1384
• Main Authors: Azar, Khadijeh K., Tani, Mayuko, Yasuda, Hideyo, Sakai, Akemi, Inoue, Masaki, Sasagawa, Toshiyuki
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cervical cancer; cervical intraepithelial lesions; Cervical Intraepithelial Neoplasia - metabolism; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; cervical secretion; cytokines; Deoxyribonucleic acid; DNA; DNA, Viral - analysis; Enzyme-Linked Immunosorbent Assay; Female; Female genital diseases; Genetic testing; Gynecology. Andrology. Obstetrics; Human papillomavirus; Humans; Interferon-gamma - metabolism; Interleukin-10 - secretion; Interleukin-6 - metabolism; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Medical screening; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Papillomavirus Infections - complications; Papillomavirus Infections - metabolism; Papillomavirus Infections - pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Sexually transmitted diseases; STD; Studies; Tumor Necrosis Factor-alpha - secretion; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Womens health
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2004.08.012

Cytokines are released in response to infection of the uterine cervix by high-risk HPV. By using enzyme-linked immunosorbent assay, we measured the levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the cervical secretions of 120 cytologically normal or equivocal and 91 abnormal Japanese women. HPV infection of the cervical cells was typed by the LCR-E7 PCR method. The HPV DNA-negative samples were classified as either normal or inflamed, and the HPV DNA-positive samples were classified as HPV positive(+) n-ormal and as low- or high-grade squamous intraepithelial lesions (SILs). Compared with the normal cervices, all of the cytokines tested were elevated in inflamed, HPV+ normal, low-grade SILs (LSIL), and high-grade SILs (HSIL). The level of IL-10 was statistically higher in LSIL, and the level of TNF-α was higher in HSIL, relative to the cytokine levels in the inflamed and HPV+ normal samples ( P < 0.05; Mann-Whitney test). Multivariate analyses confirmed that increased levels of IL-10 were associated with LSIL (relative risk [RR] = 3.9, 95% confidence interval [CI] = 1.7-8.8) and that increased levels of TNF-α (RR = 4.6, 95% CI = 1.4-15) and age older than 40 years (RR = 8.5, 95% CI = 1.3-56) were associated with HSIL. The levels of INF-γ and TNF-α (Th1-cytokines) correlated negatively with those of IL-6 and IL-10 (Th2-cytokines) in HPV+ normal and LSIL subjects, whereas no such correlation was observed for HSIL. The up-regulated secretion of IL-10 may inhibit immune responses against HPV infection in early cervical lesions, whereas up-regulated TNF-α and uncoordinated cytokine secretion (elevated both Th1 and Th2 cytokines) may reflect impaired or invalid responses in advanced stage lesions. The detection of IL-10 and TNF-α in cervical secretions may be a useful indicator of local immune responses and of the stage of the cervical lesions induced by HPV infection.