Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients.

BACKGROUND: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. METHODS: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. RESULTS: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). CONCLUSION: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.

ANTECEDENTES: La estratificación de la gravedad de una infección se basa actualmente en la puntuación SOFA (Sequential Organ Failure Assessment), que es difícil de calcular fuera de la unidad de cuidados intensivos. Los biomarcadores podrían ayudar a estratificar la gravedad de la infección en pacientes quirúrgicos. MÉTODOS: Se compararon las concentraciones de 10 biomarcadores que denotan disfunción endotelial, 22 que indican granulopoyesis de emergencia y 6 que expresan la degranulación de neutrófilos en tres grupos de pacientes de tres hospitales españoles (100 con infección, 95 con sepsis y 57 con shock séptico) en las primeras doce horas después del diagnóstico. RESULTADOS: Siete biomarcadores que expresan disfunción endotelial (proadrenomedulina, sindecan-1, trombomodulina, angiopoyetina-2, endocan-1, molécula de adhesión endotelial 1 y E-selectina) mostraron una fuerte asociación con la sepsis en comparación con la infección aislada. La proadrenomedulina presentó el valor más alto de la razón de oportunidades (odds ratio, OR) en el análisis multivariable (OR 11,53, i.c. del 95% 4,15-32,08, P = 0,006) y la mejor área bajo la curva para detectar sepsis (AUC 0,86, i.c. del 95% 0,80-0,91, P < 0,001). En la comparación entre sepsis y shock séptico, los biomarcadores que mostraron la asociación más estrecha con el shock séptico fueron dos biomarcadores de degranulación de neutrófilos (proteinasa-3 y lipocalina-2) (OR 8,09, i.c. del 9% 1,34-48,91, P = 0,028; OR 6.62, i.c. del 95% 2,47-17,77, P = 0,002), pero la lipocalina-2 presentó la mejor AUC (0,81, i.c. del 95% 0,73-0,90, P < 0,001). CONCLUSIÓN: la proadrenomedulina y la lipocalina-2 podrían representar alternativas a la puntuación SOFA para detectar sepsis y shock séptico en pacientes quirúrgicos con infección.

Clinical factors influencing mortality risk in hospital-acquired sepsis.

BACKGROUND: Identification of factors that confer an increased risk of mortality in hospital-acquired sepsis (HAS) is necessary to help prevent, and improve the outcome of, this condition. AIM: To evaluate the clinical characteristics and factors associated with mortality in patients with HAS. METHODS: Retrospective study of patients with HAS in a major Spanish Hospital from 2011 to 2015. Data from adults receiving any of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes associated with sepsis were collected. Those fulfilling the SEPSIS-2 definition with no evidence of infection during the first 48 h following hospitalization were included (N = 196). Multivariate analysis was employed to identify the risk factors of mortality. FINDINGS: HAS patients were found to have many of the risk factors associated with cardiovascular disease (male sex, ageing, antecedent of cardiac disease, arterial hypertension, dyslipidaemia, smoking habit) and cancer. Vascular disease or chronic kidney disease were associated with 28-day mortality. Time from hospital admission to sepsis diagnosis, and the presence of organ failure were risk factors for 28-day and hospital mortality. Experiencing more than one episode of sepsis increased the risk of hospital mortality. 'Sepsis code' for the early identification of sepsis was protective against hospital mortality. CONCLUSION: This study identifies several major factors associated with mortality in patients suffering from HAS. Implementation of surveillance programmes for the early identification and treatment of sepsis translate into a clear benefit.

Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis.

OBJECTIVE: The impact of endogenous immunoglobulin isotypes on the prognosis of patients with severe sepsis has not been sufficiently explored. The aim of this study was to evaluate the association between immunoglobulin levels in plasma and survival in patients with this condition. DESIGN AND PATIENTS: A prospective multicentre cohort study was conducted. A total of 172 adult patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock were recruited. Patients were classified based on deciles of immunoglobulin concentrations at diagnosis of sepsis. Categorical variables were created and tested for their association with survival during hospitalization in the ICU. RESULTS: Overall, 42 patients died in the ICU during the study. Kaplan-Meier analysis showed that immunoglobulin concentrations below 300 mg dL(-1) for IgG1, 35 mg dL(-1) for IgM and 150 mg dL(-1) for IgA were associated with shorter survival times. Multivariate regression analysis showed that IgG1 < 300 mg dL(-1) was a risk factor for mortality [odds ratio (OR) 2.50, 95% confidence interval (CI) 1.04-6.03; P = 0.042]. The combined presence of IgG1, IgM and IgA levels below the described thresholds had a synergistic impact on mortality risk (OR 5.27, 95% CI 1.41-19.69; P = 0.013). A similar effect was observed for combined low levels of IgG1 and IgA (OR 4.10, 95% CI 1.28-13.12; P = 0.018) and also of IgG1 and IgM (OR 3.10. 95% CI 1.13-8.49; P = 0.028). CONCLUSIONS: The combined presence of low levels of the endogenous immunoglobulins IgG1, IgM and IgA in plasma is associated with reduced survival in patients with severe sepsis or septic shock. Assessment of the concentrations of these immunoglobulins could improve the results of treatment with exogenous immunoglobulins in patients with sepsis.

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia.

PURPOSE: To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia. METHODS: Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain. RESULTS: Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4-20) vs. 10 (IQR 5-20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55-1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58-1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44-1.35, p = 0.4). CONCLUSION: Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.

Tendencia y estacionalidad del virus respiratorio sincitial en Valladolid durante el periodo 1993-2010 / Trend and seasonality of respiratory syncytial virus in Valladolid (Spain) during 1993-2010

Objetivo: Describir la tendencia y la estacionalidad de las infecciones por el virus respiratorio sincitial (VRS) en el Área de Salud de Valladolid Este durante el periodo 1993-2010.Pacientes y métodos: Se incluyeron en el estudio las muestras analizadas entre enero de 1993 y diciembre de 2010 por el Servicio de Microbiología e Inmunología del Hospital Clínico Universitario de Valladolid. Las muestras se clasificaron en función de la edad del paciente y el método de diagnóstico. El análisis virológico se llevó a cabo mediante técnicas de diagnóstico rápido, cultivo celular o microarrays. Se calcularon las tasas anuales referidas al área cubierta por el hospital para identificar la tendencia desde 1993 hasta 2010. Los meses epidémicos se establecieron mediante el índice epidémico, y la periodicidad mediante el método cosinor. Resultados: De 4.103 muestras analizadas de pacientes con síntomas respiratorios, en 1.644 (40,1%) se confirmó la presencia de VRS. Casi el 90% de los casos confirmados se dieron en pacientes menores de 2 años, y el 59,5% en menores de 1 año. Las tasas fluctuaron cada 2-4 años, alcanzando valores máximos en 2002 y 2003, con 41,5 y 44,9 casos por 100.000 habitantes-año, respectivamente. Aunque se produjeron casos durante todo el año, los periodos epidémicos se dieron entre septiembre y marzo, detectándose la mayor incidencia en enero y la menor en julio. Conclusiones: Los datos epidemiológicos (prevalencia del virus en muestras respiratorias y distribución por edad) fueron similares a los descritos en otros estudios. Los periodos epidémicos se describieron entre septiembre y marzo, alcanzado el máximo de incidencia en enero y el mínimo en julio. A pesar de ello, a lo largo de los 18 años estudiados sólo en 5 años no hubo circulación de VRS durante 2-3 meses, y en 8 más el VRS estuvo ausente durante un mes. No hay ningún dato que permita anticipar la ausencia de circulación del virus, aspecto importante para la profilaxis de esta infección (AU)

Purpose: The aim of the study is to describe the trend and seasonality of respiratory syncytial virus (RSV) infections in the East Valladolid Health Administrative-Division during the period1993-2010.Patients and Methods: Samples processed in the area of Eastern Valladolid by the Department of Microbiology and Immunology at the Hospital Clínico Universitario of Valladolid between January 1993 and December 2010 were included in the analysis. Cases were classified by age and diagnostic method. Virological diagnosis of the cases was carried out through rapid assay methods, shell-vial cell culture assay or microarray techniques. Annual rates were calculated to identify the trend of the infection from 1993 to 2010. The epidemic index was used to establish epidemic months and cosinor method to evaluate periodicity. Results: From 4,103 samples processed, collected from patients with respiratory symptoms, 1,644 (40.1%) were confirmed to be RSV possitive. Almost 90% of the confirmed cases appeared in patients under 2 years old, 59.5% in younger than1 year old children. The infection trend seems to fluctuate every 2-4 years with higher rate in 2002 and 2003, accounting for 41.5 and 44.9 cases detected per 100,000 inhabitants-year, respectively. Although cases were detected throughout all the year, epidemic periods were detected from September to March with highest values in January and lowest values in July. Conclusions: Epidemiological data (VRS prevalence in respiratory samples and distribution of cases by age) was similar to those obtained in previous studies. Epidemic periods were described from September to March with the highest numbers of cases in January and lowest values in July. In spite of this, along the eighteen years studied there were eight years without RSV detection in one month and only five years without detection in 2-3 months. There is no data that allows to predict the lack of circulation for RSV, being an important factor for the prophylaxis of the infection (AU)

Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: A pilot study

Introduction: It remains unknown why some intubated patients remain infection-free while others develop tracheobronchitis (VAT) or pneumonia (VAP). Objective: To identify and compare VAP/VAT gene expression "signatures" using genome-wide oligonucleotide microarrays. Material and methods: A prospective translational study of gene expression profiles of VAP and VAT groups was carried out, establishing comparisons in both pre-infection and infection phases. Pathway and functional analyses were performed with Ingenuity Pathway Analysis (IPA). Data analysis and hierarchical clustering of the genes involved in the signalling pathways expressed differentially in the two groups were performed with GeneSpring GX 11.0. Results: Eight patients developing respiratory infections (3 VAP and 5 VAT) after 4 days of mechanical ventilation were assessed. Comparison of gene expression profiles in the pre-infection period revealed 5595 genes expressed differentially between VAP and VAT (p<0.01, fold change >2). Comparative IPA analysis identified a significant depression of the complement system signalling pathway in the VAP group, affecting the classical pathway along with the final common pathway (p<0.05). In addition, the cAMP and calcium signalling pathways were also significantly depressed in the VAP group during the pre-infection phase also. Conclusion: Intubated patients complicated with pneumonia developed immune impairment in the pre-infection period, manifesting as a relatively lower expression of genes involved in the complement system that differed from patients developing tracheobronchitis. These findings suggest that a significant proportion of VAP episodes cannot be prevented, but might be treatable through pre-emptive therapy (AU)

Introducción: Seguimos sin saber por qué algunos pacientes intubados no sufren infecciones mientras que otros presentan traqueobronquitis (TAV) o neumonía (NAV). Objetivo: Identificar y comparar los patrones de la expresión genética de la NAV/TAV usando micromatrices multigénicas oligonucleotídicas. Material y métodos: Se realizó un estudio aplicado prospectivo de los patrones de la expresión genética de los grupos con NAV y TAV, estableciendo comparaciones tanto en la fase previa a la infección como en la fase infecciosa. Se realizaron análisis de vías y funcionales con Ingenuity Pathway (IPA). Los análisis de datos y el agrupamiento jerárquico de los genes implicados en las vías de señalización expresados de forma diferenciada en ambos grupos se realizaron con GeneSpring GX 11.0. Resultados: Se evaluaron ocho pacientes que presentaron infecciones respiratorias (3 NAV y 5 TAV) después de 4 días con la ventilación mecánica. La comparación de los perfiles de la expresión genética durante el período previo a la infección reveló 5.595 genes expresados de forma diferenciada entre la NAV y la TAV (p<0,01, cambio múltiplo>2). Los análisis comparativos de los IPA identificaron una depresión importante de la vía de señalización del sistema del complemento en el grupo con NAV, que afectó a la vía clásica además de a la vía común final (p<0,05). Por otra parte, el monofosfato cíclico de adenosina y las vías de señalización del calcio también se vieron muy deprimidos en el grupo (..)(AU)

Respuesta inmune respiratoria al año de vida en el niño prematuro / Respiratory immune response in first year of a preterm infant

Introducción: Existe un gran desconocimiento acerca de la evolución del sistema inmune en la mucosa respiratoria del niño prematuro a largo plazo. La inmadurez y las infecciones respiratorias pueden influir sobre la respuesta inmune de las mucosas. El propósito de este estudio era evaluar la secreción respiratoria de los mediadores inmunológicos al año de vida en niños prematuros. Pacientes y métodos: Desde octubre de 2008 hasta abril de2009 se reclutaron 77 prematuros nacidos en 6 servicios de pediatría de Castilla y León, así como 14 controles sanos a término. Los prematuros fueron citados al año de edad gestacional corregida y los niños a término al año de vida, momento en el cual se les realizó un lavado nasal para determinar los niveles de 27 mediadores inmunológicos mediante un ensayo de Biorad®. Resultados: Los niños prematuros tenían niveles más elevados de quimiocinas (eotaxina, IP-10), citocinas Th-1 (IFN-epsilon), Th-2 (IL-13), Th-17 (IL-17) y factores de crecimiento celular (PDGF-bb, VEGF, FGF-b, G-CSF y GM-CSF) que los niños a término. Cuando se compararon los niveles de mediadores entre los niños que habían recibido profilaxis para el virus respiratorios incitial con palivizumab y los que no, los segundos tenían niveles significativamente más altos de MCP-1, IL-1RA, IL-10,IL-12p70 y VEGF (p <0,05) que los primeros. Conclusiones: Este trabajo demuestra por vez primera la influencia de la prematuridad sobre los perfiles de secreción respiratoria de las citocinas y quimiocinas a largo plazo. Por otra parte, nuestros resultados indican que la evaluación del impacto de la profilaxis de la infección respiratoria es un camino interesante para comprender la maduración de la respuesta inmune de la mucosa respiratoria del prematuro(AU)

Introduction: There is a big unawareness about a long term respiratory mucous immune system evolution in the preterm infant. Immaturity and respiratory infections can have a big influence on the mucous immune responses. This investigation’s purpose is the evaluation of respiratory secretion of inflammatory immunological mediators in the first year of a preterm infant. Patients and methods: Between October 2008 and April 2009, 77 preterm infants were born in 6 pediatric services of Castilla y Leon, plus to another 14 healthy controls results. Children were invited on their first corrected gestational age and the ones of healthy controls results. Nasal washing were applied to determine 27 immunological mediators’ levels by applying a Biorad test. Results: The preterm infants has higher chemokine (eotaxin,IP-10), cytokines Th-1 (IFN-epsilon), Th-2 (IL-13), Th-17 (IL-17) and cell growing factors (PDGF-bb, VEGF, FGF-b, G-CSF and GM-CSF)levels than a healthy control results children. When a comparison was made between children that received prophylaxis for their respiratory syncytial virus with palivizumab and the ones that did not receive it, the second group showed higher MCP-1, IL-1RA, IL-10, IL-12p70 and VEGF (p <0,05) levels. Conclusions: This work proves, for the first time, the influence of the premature birth on chemokine and cytokines respiratory secretion levels in a long term concepts. On other hand, our results indicate that prophylaxis impact in the respiratory infection is an interesting way to understand respiratory mucous immune response maturation in the preterm infant(AU)

Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: a pilot study.

INTRODUCTION: It remains unknown why some intubated patients remain infection-free while others develop tracheobronchitis (VAT) or pneumonia (VAP). OBJECTIVE: To identify and compare VAP/VAT gene expression "signatures" using genome-wide oligonucleotide microarrays. MATERIAL AND METHODS: A prospective translational study of gene expression profiles of VAP and VAT groups was carried out, establishing comparisons in both pre-infection and infection phases. Pathway and functional analyses were performed with Ingenuity Pathway Analysis (IPA). Data analysis and hierarchical clustering of the genes involved in the signalling pathways expressed differentially in the two groups were performed with GeneSpring GX 11.0. RESULTS: Eight patients developing respiratory infections (3 VAP and 5 VAT) after 4 days of mechanical ventilation were assessed. Comparison of gene expression profiles in the pre-infection period revealed 5595 genes expressed differentially between VAP and VAT (p<0.01, fold change >2). Comparative IPA analysis identified a significant depression of the complement system signalling pathway in the VAP group, affecting the classical pathway along with the final common pathway (p<0.05). In addition, the cAMP and calcium signalling pathways were also significantly depressed in the VAP group during the pre-infection phase also. CONCLUSION: Intubated patients complicated with pneumonia developed immune impairment in the pre-infection period, manifesting as a relatively lower expression of genes involved in the complement system that differed from patients developing tracheobronchitis. These findings suggest that a significant proportion of VAP episodes cannot be prevented, but might be treatable through pre-emptive therapy.

Higher constitutive IL15R alpha expression and lower IL-15 response threshold in coeliac disease patients.

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R alpha mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R alpha mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.

Síndrome respiratorio agudo grave en niños: datos clave para la fisiopatogenia, terapia, desarrollo de vacunas y control de diseminación / SARS in children: key data concerning pathophysiology, therapy, vaccine development and control of its transmission

El síndrome respiratorio agudo grave (SRAG) es una enfermedad de reciente aparición, que ha causado una gran conmoción en el mundo médico y en la sociedad en general. El agente causal es un nuevo Coronavirus, que ha demostrado cumplir los postulados de Koch. Desde nuestro punto de vista, existe una cuestión sin resolver aún en la patogenia del SRAG: ¿cuál es el responsable final del sufrimiento respiratorio: una lesión viral citopática directa en los neumocitos, una lesión mediada por el sistema inmune en respuesta contra este virus, o ambos componentes? Los datos previos procedentes de estudios en autopsias, sueros y sangre de pacientes adultos sugieren un importante componente inmunoinflamatorio. Lo corrobora también el hecho de que en niños pequeños se trata de una enfermedad con un curso mucho más leve que en adultos. Hasta la fecha, no se han registrado muertes en la población pediátrica. Este dato por sí mismo descarta que exista un efecto viral citopático directo importante: los niños serían los pacientes más afectados debido a la inmadurez de su sistema inmune; además, la gravedad es mayor en los pacientes con un sistema inmune adulto capaz de presentar una respuesta inmunoinflamatoria completa. Adicionalmente, esta observación tiene su repercusión en el desarrollo de vacunas para esta enfermedad. Se deberían evitar utilizar antígenos vacunales virales que pudieran llevar a una respuesta inmunoinflamatoria, como la que tendría lugar en el curso de la enfermedad natural. Por último, hay que estar alerta ante niños paucisintomáticos que transmitan la enfermedad a sus contactos adultos, en los cuales la enfermedad es más grave. En conclusión, los niños demuestran de nuevo que no son una reproducción a escala de un adulto, y que presentan peculiaridades que, sin embargo, pueden ayudar a comprender lo que ocurre en las enfermedades de los adultos (AU)

Enfermedades por virus lentos del sistema nervioso central: ¿un nexo fisiopatogénico común? Vías hacia nuevos enfoques terapéuticos / Slow virus diseases of the central nervous system: a common physiopathogenic nexus? Paths towards new therapeutic approaches

Las enfermedades por virus lentos del sistema nervioso central (SNC) son aquellas en las que el periodo de incubación previo a las manifestaciones clínicas es muy prolongado y se mide en meses e incluso en años. Nos proponemos revisar la concepción actual existente sobre la fisiopatogénesis de estas enfermedades, con el fin de abrir el debate sobre nuevos enfoques terapéuticos, dado el oscuro pronóstico y el escaso éxito de los tratamientos actuales para ellas. El enfoque clásico ante cualquier enfermedad infecciosa es el de actuar frente al patógeno. En este artículo expondremos el importante papel que puede desempeñar el sistema inmune en estas afecciones y, por tanto, la posibilidad de un enfoque terapéutico desde el punto de vista de la inmunomodulación. Nuestra opinión es que los pacientes quizá se beneficien de combinar la estrategia clásica antiviral (inosiplex, ribavirina, IFN-alfa) con el uso de inmunomoduladores del tipo de la pentoxifilina, o de los nuevos que se describen (hormona estimulante de los melanocitos alfa [MSH-alfa], dexanabinol). Mientras, no existan fármacos antivirales específicos de cada uno de estos patógenos, los inmunomoduladores podrían aportar un beneficio clínico como fármacos adyuvantes o paliativos. Esto supondría, no sólo una innovación en el tratamiento de estas enfermedades, sino también un cambio en la concepción del enfoque terapéutico, poniendo al sistema inmune en el mismo plano de importancia que el propio virus (AU)