Caracterización de la respuesta inmunitaria-inflamatoria sistémica a la infección respiratoria aguda. Análisis del patrón de respuesta en pacientes asmático
- Autores: María Josefina Giuffrida Villa
- Directores de la Tesis: Melchor Álvarez de Mon Soto (dir. tes.), Nereida Valero Cedeño (codir. tes.)
- Lectura: En la Universidad de Alcalá ( España ) en 2011
- Idioma: español
- Tribunal Calificador de la Tesis: Agustín Albillos Martínez (presid.), Jorge Monserrat Sanz (secret.), Francisca Monsalve del Castillo (voc.), José Antonio Girón González (voc.), Luis Berlanga González (voc.)
- Materias:
- Enlaces
- Resumen
- español
El patrón de citoquinas en pacientes adultos asmáticos con IRA, y su asociación con el agente etiológico y la expresión clínica de la enfermedad aún no han sido bien establecidos. Para estudiar el patrón de citoquinas circulantes proinflamatorias (IL-1[beta], TNF[alfa]), de la inmunidad adaptativa (IL-4, IL-5) y quimiocinas (IL-8, MCP-1 y RANTES) en pacientes con IRA y su asociación con el agente etiológico y la expresión clínica de la enfermedad, se escogieron 39 pacientes con IRA de no más de cinco días de evolución, sin distinción de sexo, en edades comprendidas entre 18 y 65 años. 10 sujetos sanos (sin IRA y sin asma) que resultaron negativos a las pruebas virológicas y bacteriológicas sirvieron como población control. Para la investigación se tomó simultáneamente a cada paciente una muestra de sangre y de lavado nasofaringeo (LNF) o exudado faringeo (EF). En el suero se midieron los niveles de citoquinas por ELISA [pg/ml]. Las muestras de LNF o EF sirvieron para la detección viral por IFD (VSR, parainfluenza, adenovirus, influenza), y para la identificación de bacterias por métodos convencionales. Los datos fueron analizados por ANOVA con post prueba de Bonferroni?s (p< 0,05 = significativos) y los resultados fueron expresados en promedio +- desviación estándar. Se produce una respuesta sistémica con elevación de los niveles circulantes de IL-1[beta] y TNF[alfa], que no está determinada por la localización bronquial o alveolar de la infección, y es más intensa en las de causa viral. Se asocia también a un incremento de los niveles séricos de IL-4 e IL-5 que no está determinada por la localización bronquial o alveolar, ni por la naturaleza vírica o bacteriana de las infecciones. La intensidad y el patrón de respuesta sistémica con elevación de IL-1[beta], TNF[alfa], IL-4 e IL-5 en pacientes con IRA, no se modifica de forma biológicamente relevante por la condición de asmático del paciente. Se produce una respuesta sistémica con elevación de los niveles circulantes de quimioquinas MCP-1 y RANTES, y normalidad de los IL-8, que se observa de forma selectiva en los pacientes asmáticos, y de forma preferente, en los de etiología viral de la infección. La inoculación de los virus causales de la IRA's a cultivos de células mononucleares, induce la producción de citoquinas IL-1[beta], TNF[alfa], IL-4, IL-5 y selectivamente de la quimioquina MCP-1, sin objetivarse la de IL-8 y RANTES.
- English
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.
- español
