Changes and significances of inflammatory cytokines and chemokines in cervical secretions of patients with human papillomavirus infected cervical intraepithelial neoplasia
Objective To observe the changes of inflammatory cytokines and chemokines in serum and cervical secretions of patients with cervical intraepithelial neoplasia(CIN)infected with human papillomavirus(HPV),and to investigate the influencing factors of high-grade squamous intraepithelial lesion(HSIL)in patients with HPV infected CIN.Methods Ninety HPV infected CIN patients in the First Affiliated Hospital of Xinjiang Medical University from March 2022 to May 2023 were divided into 65 patients with CIN grade Ⅰ[low-grade squamous intraepithelial lesion(LSIL)group]and 25 patients with CIN grade Ⅱ-Ⅲ(HSIL group).The age,body mass index(BM1),course of HPV infection,and rates of hypertension,fertility and abortion were compared between two groups.The CD3+T lymphocytes,CD4+T lymphocytes and CD8+T lymphocytes in peripheral blood were detected by flow cytometry,and the CD4+/CD8+ratio was calculated.The levels of interleukin(IL)-2,IL-4,IL-10,interferon-γ(IFN-γ),chemokine C-C motif ligand(CCL)2,CCL22,chemokine CXC motif ligand(CXCL)8 and CXCL16 in serum and cervical secretions were measured by ELISA method,and multivariate logistic regression was used to analyze the influencing factors of HSIL in patients with HPV infected CIN.Results(1)There were no significant differences in the age,BMI,course of HPV infection,and rates of hypertension,fertility and abortion between two groups(P>0.05).(2)The levels of IL-4,IL-10,CCL2 and CCL22 in serum and cervical secretions were lower in HSIL group[(8.01±2.38),(2.63± 1.26)ng/L;(30.44±6.19),(8.68±3.28)ng/L;(15.47±7.16),(4.62±2.45)ng/L;(2.89±1.10),(0.73± 0.45)ng/L]than those in LSIL group[(9.23±2.12),(3.48±1.28)ng/L;(33.29±4.21),(10.13±1.90)ng/L;(18.49±3.98),(6.11±2.46)ng/L;(3.52±1.22),(0.98±0.35)ng/L](P<0.05),the levels of CXCL16 were higher in HSIL group[(11.66±2.71),(4.91±1.22)ng/L]than those in LSIL group[(9.58±2.58),(3.71± 1.38)ng/L](P<0.05),and there were no significant differences in the levels of IL-2,IFN-γ and CXCL8 between two groups(P>0.05).(3)The percentage of CD4+T lymphocytes and the ratio of CD4+/CD8+were lower in HSIL group[(27.40±3.51)%,1.04±0.16]than those in LSIL group[(30.25±4.55)%,1.12±0.13](P<0.05),the percentage of CD8+T lymphocytes was higher in HSIL group[(31.60±4.40)%]than that in LSIL group[(29.56±3.75)%](P<0.05),and there was no significant difference in the percentage of CD3+T lymphocytes between two groups(P>0.05).(4)The percentage of CD4+T lymphocytes(OR=0.804,95%CI:0.661-0.977,P=0.029),serum IL-4(OR=0.672,95%CI:0.464-0.972,P=0.035),serum IL-10(OR=0.786,95%CI:0.660-0.937,P=0.007),IL-4 level in cervical secretions(OR=0.688,95%CI:0.362-0.908,P=0.024),IL-10 in cervical secretions(OR=0.754,95%CI:0.559-0.916,P=0.043),CCL2 in cervical secretions(OR=0.845,95%CI:0.675-0.923,P=0.042),CCL22 in cervical secretions(OR=0.792,95%CI:0.011-0.851,P=0.026),and CXCL16 in cervical secretions(OR=1.341,95%CI:1.059-2.369,P=0.012)were the influencing factors of HSIL in patients with HPV infected CIN.Conclusion The HPV infected CIN patients with low percentage of CD4+T lymphocytes,low levels of IL-4 and IL-10 in serum and cervical secretions,low levels of CCL2 and CCL22 in cervical secretions,and high level of CXCL16 in cervical secretions have a high risk of HSIL.