Caracterización del estado funcional del sistema inmunitario en individuos de diferente entorno geográficoanálisis del impacto de la infección crónica asintomática por virus B

  1. Monsalve del Castillo, Francisca
Supervised by:
  1. Melchor Álvarez de Mon Soto Director
  2. Agustín Albillos Martínez Director
  3. Tania Romero Adrian Director

Defence university: Universidad de Alcalá

Fecha de defensa: 24 June 2008

Committee:
  1. Manuel Rodríguez Zapata Chair
  2. Eduardo Reyes Martín Secretary
  3. M. Puerto Hernandez Fuentes Committee member
  4. José Antonio Girón González Committee member
  5. José Luis Calleja Panero Committee member

Type: Thesis

Abstract

Infection by the hepatitis B virus (HBV) is a disease that has affected humanity since the beginning of its history. Because it is a non-cytopathic virus, its capacity to create lesions and progress toward chronicity is conditioned by the immunological reaction, basically of cellular type, determined by the host’s capacity to eliminate the viral particle from the infected hepatocytes; the degree of hepatocellular damage that follows varies according to the immune system reaction of the affected individual. In this context the study of the cytokines in certain pathologies improves the understanding of their participation as mediators in the immune reaction. Various studies have evaluated the association between exposure to the environment and the development of different clinical-pathological entities, revealing influences of the environment on the immune system. To further the knowledge about B virus infection and the impact the geographical environment and epidemiologic could have the functional state of the immune system was studied in individuals not infected and chronically infected by of HBV belonging to different geographical areas from Venezuela and Spain, by quantifying the circulating cytokines (IL-2, IL-6, IL-10, IL-12, IL-18, TNF-α and IFNγ). Serologic marker detection for chronic asymptomatic HBV infection and serologic cytokine determination were made using commercial ELISA techniques. Significant differences were found among the groups studied. Indigenous people not infected by HBV evidenced the predominant phenotype Th2 ( IL-6, IL-10 and TNF-α) with a decrease in IFN-γ, they differed from urban, non-infected Venezuelans in whom the predominant cytokine was IFN-γ with a decrease in the alert cytokines (IL-6, IL-10 and TNF-α). In NI-HBV Spaniards, a significant increase in IL-6 with non-detectable IL-2 (Th1) and decreased IL-10 were noted. For indigenous carriers and their non-infected equivalents, cytokines showed similar behavior. In urban Venezuelan carriers, significant serum levels of IL-2 (Th1) and the cytokines IL-6, IL-10 and TNF- α (Th2) were present. This study has demonstrated that differences in serum levels exist for the cytokines measured in groups from different geographical surroundings (Spain and Venezuela). Geographical location and environmental and socio-cultural factors can be noted in the different serum concentration patterns for circulating cytokines. The impact of chronic hepatitis B virus infection is associated with different variation patterns in the serum cytokine concentrations in native or urban Venezuelan patients. Therefore, exogenous factors exist that condition the functional state of the immune system in healthy subjects and those who demonstrate evidence of chronic infection, indicating that normality margins for analytic immunological variables should be adapted to the populations under study.