Caracterización de la respuesta inmunitaria-inflamatoria sistémica a la infección respiratoria aguda. Análisis del patrón de respuesta en pacientes asmático

  1. Giuffrida Villa, María Josefina
Supervised by:
  1. Melchor Álvarez de Mon Soto Director
  2. Nereida Valero Cedeño Co-director

Defence university: Universidad de Alcalá

Fecha de defensa: 21 July 2011

Committee:
  1. Agustín Albillos Martínez Chair
  2. Jorge Monserrat Sanz Secretary
  3. Luis Berlanga González Committee member
  4. Francisca Monsalve del Castillo Committee member
  5. José Antonio Girón González Committee member
Department:
  1. Medicina y Especialidades Médicas

Type: Thesis

Abstract

Among the postulated mechanisms inducing asthma, the viruses are triggers, especially the child population for which there is abundant research on the immune mechanisms involved in this response, but, the immunological mechanisms associated with asthma in adults with viral Acute Respiratory Infection (ARI) and coinfection (mixed infection: viral and bacterial), have not yet been well established. Therefore, the objective of the present study was, to measure serum proinflammatory cytokines (IL-1 , TNF ), Th2 (IL-4, IL-5) and chemokines (IL-8, MCP-1 and RANTES) in individuals with ARI (viral and mixed infections), so as to determine the cytokines pattern involved in this response. In addition, it seeks to explain the systemic response of the virus in vitro, using cultured peripheral blood mononuclear cells (PBMC). For the study 43 individuals were selected from 161 who attended the various clinics in the city centers with symptoms suggestive of ARI. The subjects were adult asthmatic and non asthmatic with IRA of not more than 5 days of evolution, without distinction of sex, and ages 18 to 65 years, who were not receiving antibiotic treatment and/or steroid. 10 healthy patients uninfected were used as control population. Samples of nasopharyngeal wash and throat swabs were used to detect viruses and/or bacteria, and serum samples to measure cytokine by ELISA; the cytokines were also measured in PBMC cultures prepared from whole blood from healthy subjects. The results were analyzed by ANOVA using Bonferroni’s post test. There is a systemic response, with elevated circulating levels of IL-1 and TNF , which is not determined by the location of the bronchial alveolar infection, and is more intense in the viral cause. There is a systemic response with elevated serum levels of IL-4 and IL-5 which is not determined by the location of the bronchial alveolar or by the nature of viral or bacterial infections. The intensity and pattern of systemic response with elevated IL-1 , TNF , IL-4 and IL-5 in patients with ARI, were not so lighly biologically modified by the patient's asthmatic condition. There was a systemic response with elevated circulating levels of chemokines MCP-1 and RANTES, and normality of the IL-8, which occurs selectively in patients with asthma, and preferably, with a viral infection. The inoculation of the causal virus IRAs to cultures of mononuclear cells, induced the production of cytokines IL-1 , TNF , IL-4, IL-5 and selectively chemokine MCP-1, without a demonstrable IL- 8 and RANTES. Our data demonstrate that the ARI’s has a significant impact at the systemic inflammatory immune system. It should be noted that the patients included in our study did not fulfill criteria of severity to require hospitalization, and none had a complication caused during the treatment phase, and there was no mortality. Therefore, this impact is evident even in patients with acute non-serious infection. It is also interesting to note that the biological characteristics of the systemic impact have certain features related to the etiological factor, being more intense in the viral infection. Our status also shows that the virus causing the IRA are responsable for causing an intense activation of PBMC with increased production of citoquines and chemokines analyzed in vivo. Therefore, the aforementioned more intense systemic response in ARI caused by infection may be a step for the viral particles to go into peripheral blood. The relevance of the host response does not seem that was significantly influenced by the condition of being asthmatic. That is, the stimulus intensity capable of causing disease is an immune response/inflammatory systemic similar in asthmatics and non-asthmatic Th2 conditioning overcoming the possible operating in those. The intensity of the systemic response and production of mediators, can lead to the development of new therapeutic strategies that inhibit these molecules and reduce their overall impact.