Quantitative analysis of IL-10 and IFN-? mRNA levels in normal cervix and human papillomavirus type 16 associated cervical precancer

Abstract

Human papillomavirus type 16 is a major factor in cervical carcinogenesis. Inappropriate cytokine synthesis may direct the local immune response away from a type‐1 (cellular) pattern and may subsequently contribute to the development and progression of precancer. Quantitative reverse transcription–polymerase chain reaction (RT‐PCR) using a competitive mimic was carried out to determine type‐1 (interferon gamma (IFN‐γ)) and type‐2 (interleukin‐10 (IL‐10)) cytokine mRNA levels in whole cervical specimens (without microdissection) from seven normal and nine HPV‐16 positive CIN formalin‐fixed paraffin‐embedded tissues. Microdissection was used to measure separately the epithelial and sub‐epithelial levels of IFN‐γ and IL‐10 mRNAs in 11 specimens of normal cervix and 25 HPV‐16 positive CIN (nine CIN 1, seven CIN 2 and nine CIN 3). IFN‐γ mRNA was lower in CIN than normal (p=0.04). IL‐10 mRNA level in CIN was significantly higher (p=0.005) than in normal cervix (before microdissection). Epithelial IFN‐γ mRNA showed a significant decrease in all grades of CIN (median=3.58) compared with normal (7.74) (ppp=0.005 and 0.0005, respectively). IL‐10 was detected in the epithelium of only one of 11 normal and one of 25 CIN, but sub‐epithelial IL‐10 was significantly higher in CIN 2 (0.08) and CIN 3 (0.26) than in normal (0.00) (p=0.036 and 0.0032, respectively). There was no significant difference in the sub‐epithelial level of IL‐10 between normal and CIN 1 (0.00) (p=0.96). Our results suggest that reduced epithelial and sub‐epithelial IFN‐γ, as well as increased sub‐epithelial IL‐10 synthesis may play a role in the development and progression of HPV‐16 associated cervical precancer. Copyright © 2001 John Wiley & Sons, Ltd.