interleukin-8 and Anus-Neoplasms

We analysed local cellular and humoral immunity factors in the anal mucosa in an attempt to explain how HIV infection increases the risk of anal cancer in HPV-infected patients.. HIV-positive cases and matched HIV-negative controls with more than one recurrence of condylomas were included in a prospective study following treatment of the initial lesions. Patients were followed every 3 to 6 months for the development of anal intraepithelial neoplasia (AIN3) and cancer for up to 60 months. Tissue CD1a(+), CD3(+), CD4(+), CD8(+) cells and mRNAs of selected cytokines and chemokines were quantified and compared in patients with or without AIN3 or cancer using morphometric or immunohistochemistry analysis and qRT-PCR.. Sixty-six individuals (22 patients and 44 controls) were included. In the case group, CD1a(+) and CD3(+) cell counts were significantly lower in biopsies from AIN3 and cancer specimens compared with those from AIN 1-2 or normal biopsies (P < 0.0001). A CD1a(+) count of < 10/mm was predictive of AIN3 and cancer (Odds ratio = 9.4, 95% CI: 5.4-18.3, P < 0.0001). IL-8 and IL23 levels were significantly higher in cancer than in non-cancer tissues regardless of HIV status (P = 0.02). FoxP3 expression was significantly higher in HIV-infected cases than in controls with AIN3/cancer (P < 0.04).. Depletion of CD1a(+) and CD3(+) cells and overexpression of FoxP3 in the anal mucosa appear likely to contribute to the risk of HPV-related anal cancer in HIV-infected patients. Furthermore, overexpression of IL-8 and IL-23 in the anal mucosa might be responsible for the development of this cancer regardless of HIV status.

Topics: Adult; Anal Canal; Antigens, CD1; Anus Neoplasms; Carcinoma in Situ; CD3 Complex; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Forkhead Transcription Factors; HIV Infections; Humans; Interleukin-23; Interleukin-8; Lymphocyte Count; Male; Papillomavirus Infections; Regression Analysis; Risk Factors; RNA, Messenger