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Titolo:
IMMUNE ACTIVATION IN CERVICAL NEOPLASIA - CROSS-SECTIONAL ASSOCIATIONBETWEEN PLASMA SOLUBLE INTERLEUKIN-2 RECEPTOR LEVELS AND DISEASE
Autore:
HILDESHEIM A; SCHIFFMAN MH; TSUKUI T; SWANSON CA; LUCCI J; SCOTT DR; GLASS AG; RUSH BB; LORINCZ AT; CORRIGAN A; BURK RD; HELGESEN K; HOUGHTEN RA; SHERMAN ME; KURMAN RJ; BERZOFSKY JA; KRAMER TR;
Indirizzi:
NCI,DIV CANC EPIDEMIOL & GENET,NIH,EPN ROOM 443 BETHESDA MD 20892 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH BETHESDA MD 20892 UNIV TEXAS,SW MED SCH DALLAS TX 75235 KAISER PERMANENTE PORTLAND OR 97227 DIGENE CORP SILVER SPRING MD 20904 YESHIVA UNIV ALBERT EINSTEIN COLL MED BRONX NY 10461 TORREY PINES INST MOL STUDIES LA JOLLA CA 92121 GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL WASHINGTON DC 20037 JOHNS HOPKINS UNIV HOSP,DEPT PATHOL BALTIMORE MD 21205 USDA,BELTSVILLE HUMAN NUTR RES CTR,CAROTENOIDS RES UNIT BELTSVILLE MD20705
Titolo Testata:
Cancer epidemiology, biomarkers & prevention
fascicolo: 10, volume: 6, anno: 1997,
pagine: 807 - 813
SICI:
1055-9965(1997)6:10<807:IAICN->2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; T-CELL; RHEUMATOID-ARTHRITIS; SERUM; RESPONSES; DIFFERENTIATION; IMMUNIZATION; LYMPHOCYTES; REGRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
A. Hildesheim et al., "IMMUNE ACTIVATION IN CERVICAL NEOPLASIA - CROSS-SECTIONAL ASSOCIATIONBETWEEN PLASMA SOLUBLE INTERLEUKIN-2 RECEPTOR LEVELS AND DISEASE", Cancer epidemiology, biomarkers & prevention, 6(10), 1997, pp. 807-813

Abstract

In a previous study (Tsukui et al., Cancer Res., 56: 3967-3974, 1996), we observed an inverse association between degree of cervical neoplasia and interleukin (IL) 2 production by peripheral blood mononuclear cells in response to human papillomavirus (HPV) 16 E6 and E7 peptides in vitro. This suggested that a Th1-mediated cellular immune response might be important in host immunological control of HPV infection and that a lack of such a response might predispose to progression of cervical disease. To follow up on these findings, we have conducted a cross-sectional study of women with various degrees of cervical neoplasia to investigate the association between overall immune activation and cervical disease. A total of 235 women were recruited into our study; 120 of these women were participants in our previous study in which IL-2 production in response to HPV-16-specific peptides was measured. Thestudy population included 34 women with invasive cancer, 62 women with high-grade squamous intraepithelial lesions (HSILs), and 105 women with low-grade squamous intraepithelial lesions (LSILs). In addition, 34 cytologically normal women with no past history of squamous intraepithelial lesions despite confirmed HPV-16 infection in the 5 years preceding the study were selected as controls. As our measure of overall immune activation, serum samples obtained from study participants were tested for soluble IL-2 receptor (sIL-2R) level using an ELISA method. The mean sIL-2R levels were found to increase with increasing diseaseseverity (P-trend = 0.0002). Among cytologically normal, HPV-exposed women, the mean receptor level in serum was 465.8 units/ml compared to467.6 units/ml among LSIL subjects, 514.9 units/ml among HSIL subjects, and 695.5 units/ml among women with invasive cervical cancer. Similarly, the proportion of women with elevated slL-2R levels (defined as greater than or equal to 450 units/ml) increased with increasing disease severity from 35.2% among normal study subjects to 70.6% among cancer patients (P-trend = 0.003). Among the subgroup of subjects for whomin vitro IL-2 production in response to HPV-16-specific peptides was measured, we examined the association between in vitro IL-2 productionand serum levels of sIL-2R. sIL-2R levels were higher, on average, among those women who were positive in our IL-2 production assay compared to those who were negative, but the differences did not reach statistical significance (P > 0.05). We also observed a trend of increasing slL-2R level with increasing disease severity both in women who were positive and in women who were negative for our IL-2 production assay, but the trend was only significant among those who were negative for IL-2 production (P-trend = 0.01). Results from our studies suggest thatalthough the immune system of women with cervical neoplasia is nonspecifically activated as disease severity increases, the ability of those women with HSILs or cancer to mount a Th1-mediated immune response to HPV peptides appears to decrease compared to women with LSILs or normal women infected with HPV. Increased overall activation along with decreased Th1 immune response among women with increasing cervical disease severity might be explained by an increased Th2-mediated immune response, a response that we hypothesize is ineffective in controlling the viral infection and its early cytological manifestations. Future studies should directly assess Th2-mediated responses to confirm this hypothesis. Also, future efforts should be aimed at determining whether the associations observed are causally related to disease progression or an effect of the disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/21 alle ore 08:01:20