Glycomacropeptide Protects against Inflammation and Oxidative Stress, and Promotes Wound Healing in an Atopic Dermatitis Model of Human Keratinocytes.

Keratinocytes are actively implicated in the physiopathology of atopic dermatitis (AD), a skin allergy condition widely distributed worldwide. Glycomacropeptide (GMP) is a milk-derived bioactive peptide generated during cheese making processes or gastric digestion. It has antiallergic and skin barrier restoring properties when it is orally administered in experimental AD. This study aimed to evaluate the effect of GMP on the inflammatory, oxidative, proliferative, and migratory responses of HaCaT keratinocytes in an in vitro AD model. GMP protected keratinocytes from death and apoptosis in a dose dependent manner. GMP at 6.3 and 25 mg/mL, respectively, reduced nitric oxide by 50% and 83.2% as well as lipid hydroperoxides by 27.5% and 45.18% in activated HaCaT cells. The gene expression of TSLP, IL33, TARC, MDC, and NGF was significantly downregulated comparably to control by GMP treatment in activated keratinocytes, while that of cGRP was enhanced. Finally, in an AD microenvironment, GMP at 25 mg/mL stimulated HaCaT cell proliferation, while concentrations of 0.01 and 0.1 mg/mL promoted the HaCaT cell migration. Therefore, we demonstrate that GMP has anti-inflammatory and antioxidative properties and stimulates wound closure on an AD model of keratinocytes, which could support its reported bioactivity in vivo.

Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model.

PURPOSE: Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge. Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model. METHODS: Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice. Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay. CD8+ infiltrated cells were analyzed by immunofluorescence. RESULTS: rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue. CONCLUSION: Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.

Protective Effect of Glycomacropeptide on the Inflammatory Response of U937 Macrophages.

Macrophages play crucial roles in inflammation and oxidative stress associated with noncommunicable diseases, such as cardiovascular diseases, diabetes, and cancer. Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein that contains abundant sialic acid and has shown anti-inflammatory, antioxidative, anti-obesity, and anti-diabetic properties when is orally administered. The aim of this study was to evaluate the effect of GMP on the regulation of the inflammatory response in human macrophages and the participation of sialic acid in this activity. GMP pretreatment decreased by 35%, 35%, and 49% the production of nitrites, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α, respectively, in activated human macrophages U937. The same effect was obtained when cells were pretreated with asialo GMP, and no change on the gene expression of the lectins associated with the recognition of sialic acids, SIGLEC5, 7, and 9, was induced by GMP on macrophages, which suggests that sialic acid might not be involved in this immunoregulatory effect. Interestingly, GMP increased 8.9- and 3.5-fold the gene expression of the canonical anti-inflammatory protein SOCS3 and the antioxidant enzyme HMOX1, respectively, in U937 cells. Thus, GMP exerts anti-inflammatory and antioxidative activities on activated macrophages in a sialic acid-independent manner, which might be related to its in vivo reported bioactivity.

Impact of genetic polymorphisms related to innate immune response on respiratory syncytial virus infection in children.

Respiratory syncytial virus (RSV) causes lower respiratory tract infections and bronchiolitis, mainly affecting children under 2 years of age and immunocompromised patients. Currently, there are no available vaccines or efficient pharmacological treatments against RSV. In recent years, tremendous efforts have been directed to understand the pathological mechanisms of the disease and generate a vaccine against RSV. Although RSV is highly infectious, not all the patients who get infected develop bronchiolitis and severe disease. Through various sequencing studies, single nucleotide polymorphisms (SNPs) have been discovered in diverse receptors, cytokines, and transcriptional regulators with crucial role in the activation of the innate immune response, which is implicated in the susceptibility to develop or protect from severe forms of the infection. In this review, we highlighted how variations in the key genes affect the development of innate immune response against RSV. This data would provide crucial information about the mechanisms of viral infection, and in the future, could help in generation of new strategies for vaccine development or generation of the pharmacological treatments.

Effects of a Modern Kefir on Conditions Associated with Moderate Severe Spastic Quadriparesis Cerebral Palsy.

Cerebral palsy (CP) in children constitutes a set of movement and body posture disorders caused by brain injury, which in turn is associated with a series of intestinal, respiratory, and malnutrition conditions. Twenty-four children were selected and included for the present study and subdivided into two groups: (1) children who included modern kefir (containing 12 probiotic species) in their diet; and (2) control group (not including kefir in their diet). The group supplemented with modern kefir received a beverage with multi probiotic species and the control group received commercial yogurt (which included the 2 typical lactic acid bacteria) for 7 weeks. Anthropometric variables, resting energy expenditure, presence, and diagnosis of functional digestive disorders (FDD), frequency of respiratory problems, presence of elevated C-reactive protein, differential count of leukocytes were evaluated. A significant increase in weight and height was found in the kefir group at the final time point. In addition, kefir intake promoted a significant reduction in functional constipation and stool hardness and increased the absolute value of blood lymphocytes. Since the fermented milk beverage modern kefir improves constipation, which is the most important FDD in children with CP and the nutritional and immune status, it could be considered an important strategy to improve health in these children.

The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis.

The keratinocyte (KC) is the main functional and structural component of the epidermis, the most external layer of the skin that is highly specialized in defense against external agents, prevention of leakage of body fluids and retention of internal water within the cells. Altered epidermal barrier and aberrant KC differentiation are involved in the pathophysiology of several skin diseases, such as atopic dermatitis (AD). AD is a chronic inflammatory disease characterized by cutaneous and systemic immune dysregulation and skin microbiota dysbiosis. Nevertheless, the pathological mechanisms of this complex disease remain largely unknown. In this review, we summarize current knowledge about the participation of the KC in different aspects of the AD. We provide an overview of the genetic predisposing and environmental factors, inflammatory molecules and signaling pathways of the KC that participate in the physiopathology of the AD. We also analyze the link among the KC, the microbiota and the inflammatory response underlying acute and chronic skin AD lesions.

Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles.

Mast cells (MCs) are strategically located in tissues close to the external environment, being one of the first immune cells to interact with invading pathogens. They are long living effector cells equipped with different receptors that allow microbial recognition. Once activated, MCs release numerous biologically active mediators in the site of pathogen contact, which induce vascular endothelium modification, inflammation development and extracellular matrix remodeling. Efficient and direct antimicrobial mechanisms of MCs involve phagocytosis with oxidative and non-oxidative microbial destruction, extracellular trap formation, and the release of antimicrobial substances. MCs also contribute to host defense through the attraction and activation of phagocytic and inflammatory cells, shaping the innate and adaptive immune responses. However, as part of their response to pathogens and under an impaired, sustained, or systemic activation, MCs may contribute to tissue damage. This review will focus on the current knowledge about direct and indirect contribution of MCs to pathogen clearance. Antimicrobial mechanisms of MCs are addressed with special attention to signaling pathways involved and molecular weapons implicated. The role of MCs in a dysregulated host response that can increase morbidity and mortality is also reviewed and discussed, highlighting the complexity of MCs biology in the context of host-pathogen interactions.

Lactococcus lactis NZ9000 Prevents Asthmatic Airway Inflammation and Remodelling in Rats through the Improvement of Intestinal Barrier Function and Systemic TGF-ß Production.

INTRODUCTION: The use of probiotics has been broadly popularized due to positive effects in the attenuation of aberrant immune responses such as asthma. Allergic asthma is a chronic respiratory disease characterized by airway inflammation and remodelling. OBJECTIVE: This study was aimed to evaluate the effect of oral administration of Lactococcus lactis NZ9000 on asthmatic airway inflammation and lung tissue remodelling in rats and its relation to the maintenance of an adequate intestinal barrier. METHODS: Wistar rats were ovalbumin (OVA) sensitized and challenged and orally treated with L. lactis. Lung inflammatory infiltrates and cytokines were measured, and remodelling was evaluated. Serum OVA-specific immunoglobulin (Ig) E levels were assessed. We also evaluated changes on intestinal environment and on systemic immune response. RESULTS: L. lactis diminished the infiltration of proinflammatory leucocytes, mainly eosinophils, in the bronchoalveolar compartment, decreased lung IL-4 and IL-5 expression, and reduced the level of serum allergen-specific IgE. Furthermore, L. lactis prevented eosinophil influx, collagen deposition, and goblet cell hyperplasia in lung tissue. In the intestine, L. lactis-treated asthmatic rats increased Peyer's patch and goblet cell quantity and mRNA expression of IgA, MUC-2, and claudin. Additionally, intestinal morphological alterations were normalized by L. lactis administration. Splenocyte proliferative response to OVA was abolished, and serum levels of transforming growth factor (TGF)-ß were increased by L. lactis treatment. CONCLUSIONS: These findings suggest that L. lactis is a potential candidate for asthma prevention, and the effect is mediated by the improvement of intestinal barrier function and systemic TGF-ß production.

Protective Effect of Glycomacropeptide on Food Allergy with Gastrointestinal Manifestations in a Rat Model through Down-Regulation of Type 2 Immune Response.

Glycomacropeptide (GMP) is a bioactive peptide derived from milk κ-casein with immune-modulatory and anti-inflammatory properties. Food allergy (FA) is an adverse immune reaction with a broad spectrum of manifestations. Allergen intake induces persistent intestinal inflammation and tissue damage. In this study, the anti-allergic activity of GMP was evaluated using a rat ovalbumin (OVA)-induced FA model with gastrointestinal manifestation. Rats were orally GMP treated from 3 days prior and during FA development. The severity of food anaphylaxis and diarrheal episodes, antibody production and histamine level were measured. Histopathological changes, inflammation and predominant cytokine profile at intestine were analyzed. Oral GMP intake decreased clinical signs and diarrhea severity induced by allergen, with a significant reduction in intestinal edema and expression level of IL-1ß and TNF-α. Prophylaxis with GMP also diminished serum anti-OVA IgE and IgG1, and histamine levels. GMP treatment markedly decreased eosinophil infiltration, mast cell and goblet cell hyperplasia, total IgE expression in intestine, and prevented histological changes in villi, crypts and internal muscularis layer. The treatment effectively suppressed IL-5, IL-13 and GATA3 expression and skewed the intestinal cytokine profile toward type 1 and regulatory. These results suggest that GMP may protect against FA through down-regulating the type 2 inflammatory response.

Physiopathology of food allergies.

Food allergy is adverse reaction to certain foods and it arise from a specific immune response, including reactions mediated by immunoglobulin (Ig) E, by cells, or by both. Although individuals of all ages can develop it, the pediatric population is the most affected by it; with a prevalence of 6 to 8 %. In homeostatic conditions, the organism has tolerance and regulation pathways that hinder food components from causing damage or adverse immune reactions. However, under specific conditions such as genetic predisposition, environmental factors, dietary patterns, or premature exposure to certain foods, tolerance is not developed and aberrant and excessive immune responses to food antigens happen. Understanding the complex physiopathological mechanisms that are present during the establishment and evolution of food allergies allows the identification of potential therapeutic targets and the development of more effective therapies aimed to modify the natural course of the allergy and to improve the patients' quality of life. The objective of this review is to give an updated vision of the existing knowledge about predisposition, sensitization pathways, manifestations, and therapies in IgE-mediated food allergies, delving into the molecular and cellular mechanisms of its physiopathology.

La alergia alimentaria es una reacción adversa hacia determinados alimentos, que surge de una respuesta inmune específica, incluyendo reacciones mediadas por inmunoglobulinas (Ig) E, por células o por ambos. Aunque puede desarrollarse en individuos de todas las edades, la población infantil es la más afectada, con una prevalencia de 6 a 8 %. En condiciones de homeostasis, en el organismo existen vías de regulación y de tolerancia que impiden que los componentes de los alimentos originen daño o despierten reacciones inmunológicas adversas. Sin embargo, en condiciones específicas como carga genética predisponente, factores ambientales, patrones dietarios o exposición prematura a ciertos alimentos, no se desarrolla tolerancia y acontecen respuestas inmunológicas excesivas y aberrantes a antígenos alimentarios. La comprensión de los complejos mecanismos fisiopatológicos presentes durante el establecimiento y evolución de la alergia alimentaria permite identificar blancos terapéuticos potenciales y desarrollar terapias más efectivas dirigidas a modificar el curso natural de la alergia y mejorar la calidad de vida de los pacientes. La presente revisión pretende dar una visión actualizada del conocimiento existente sobre la predisposición, vías de sensibilización, manifestaciones y tratamientos de las alergias alimentarias mediadas por IgE, profundizando en los mecanismos moleculares y celulares de su fisiopatología.

Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress.

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1ß and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.

Protective Effect of Glycomacropeptide on the Atopic Dermatitis-Like Dysfunctional Skin Barrier in Rats.

The maintenance of a healthy skin barrier is crucial to prevent and treat atopic dermatitis (AD) lesions and avoid infections. Glycomacropeptide (GMP) is a bioactive peptide that has demonstrated promising results as an anti-inflammatory and antipruritic therapy for experimental AD. This study aimed to analyze the effect of GMP on impaired cutaneous barrier-related signs in a rat model of AD lesions. AD-like dermatitis was induced on the skin by repeated topical applications of 2,4-dinitrochlorobenzene, and animals were orally administered GMP before or after AD induction. The expression of skin structural proteins and antimicrobial peptides (AMPs) was evaluated by immunoblot or immunohistochemistry, epidermal thickening was evaluated by histochemistry, the level of IFN-γ and changes in the microbiota were evaluated by quantitative polymerase chain reaction, and the quantity of fecal short-chain fatty acids (SCFAs) was evaluated by gas chromatography. GMP administration significantly increased filaggrin, ß-defensin 2, and cathelicidin-related AMP expression in AD-like lesions. Involucrin expression was not modified. In GMP-treated animals, epidermal thickening and IFN-γ expression were strongly reduced in damaged skin. GMP treatment impacted the skin microbiota and prevented Staphylococcus aureus colonization, which is associated with AD. In addition, high levels of Bifidobacterium were detected in the feces of GMP-treated animals, and the acetic acid and butyric acid contents increased in animals prophylactically administered GMP. These results suggest that GMP markedly prevents or reverses skin barrier damage in rat AD-like lesions through a bifidogenic effect that induces fecal SCFA production with prolonged treatment. Our findings provide evidence that GMP may represent an optimum strategy for the therapy of the dysfunctional cutaneous barrier in AD.

Glycomacropeptide Bioactivity and Health: A Review Highlighting Action Mechanisms and Signaling Pathways.

Food-derived bioactive peptides are reported as beneficial and safe for human health. Glycomacropeptide (GMP) is a milk-protein-derived peptide that, in addition to its nutritional value, retains many biological properties and has therapeutic effects in several inflammatory disorders. GMP was shown under in vitro and in vivo conditions to exert a number of activities that regulate the physiology of important body systems, namely the gastrointestinal, endocrine, and immune systems. This review represents a comprehensive compilation summarizing the current knowledge and updated information on the major biological properties associated with GMP. GMP bioactivity is addressed with special attention on mechanisms of action, signaling pathways involved, and structural characteristics implicated. In addition, the results of various studies dealing with the effects of GMP on models of inflammatory diseases are reviewed and discussed.

Glycomacropeptide Attenuates Inflammation, Pruritus, and Th2 Response Associated with Atopic Dermatitis Induced by 2,4-Dinitrochlorobenzene in Rat.

Atopic dermatitis (AD) is one of the most common skin diseases, whose incidence is increasing in industrialized countries. The epicutaneous application of a hapten, such as 2,4-dinitrochlorobenzene (DNCB), evokes an experimental murine AD-like reaction. Glycomacropeptide (GMP) is a dairy bioactive peptide derived from hydrolysis of κ-casein by chymosin action. It has anti-inflammatory, prebiotic, and immunomodulatory effects. The present study was aimed to investigate the effect of GMP administration on DNCB-induced AD in rats. The severity of inflammatory process, pruritus, production of cytokines, and total immunoglobulin E (IgE) content were measured, and the histopathological features were analyzed. GMP reduced the intensity of inflammatory process and edema of DNCB-induced dermatitis, with a significant decrease in eosinophils recruitment and mast cells hyperplasia. In addition GMP suppressed the serum levels of total IgE and IL-4, IL-5, and IL-13 expression in AD-lesions. Besides, the levels of IL-10 were significantly increased. Remarkably, GMP administration before AD-induction abolished pruritus in dermatitis-like reactions in the rats. Taken together, these results indicate that GMP has an inhibitory effect on AD by downregulating Th2 dominant immune response, suggesting GMP as a potential effective alternative therapy for the prevention and management of AD.

Glycomacropeptide administration attenuates airway inflammation and remodeling associated to allergic asthma in rat.

OBJECTIVE: Glycomacropeptide (GMP) is a bioactive peptide derived from milk that has been reported to exhibit a range of anti-inflammatory and immunomodulatory properties. The aim of this study was to analyze the prophylactic effect of GMP administration on airway inflammation and remodeling in an experimental model of asthmatic rat. METHODS: Animals treated orally with or without GMP (500 mg/kg/day) were ovalbumin-sensitized and -nebulized and several indicators of Th2 response, airway structural changes and inflammatory cells recruitment were evaluated. RESULTS: Treatment with GMP prior and during asthma development resulted in reduction of allergen-specific IgE titers in serum and blood eosinophilia. Also, GMP substantially suppressed the recruitment of inflammatory cells to bronchoalveolar compartment. Histological studies demonstrated that GMP markedly inhibits eosinophils infiltration, goblet cells hyperplasia and collagen deposit in lung tissue. The latter effect was related with an inhibition in transforming growth factor-ß expression. In addition, expression of interleukin-5 and -13 were substantially inhibited in lung while that of interleukin-10 was increased. CONCLUSION: Our results suggest that administration of GMP may prevent the development of an excessive Th2 response in asthma and effectively ameliorates the progression of the disease.

Novel Mechanisms Underlying the Therapeutic Effect of Glycomacropeptide on Allergy: Change in Gut Microbiota, Upregulation of TGF-ß, and Inhibition of Mast Cells.

BACKGROUND: The prevalence of allergic diseases is globally increasing. We have previously described that glycomacropeptide (GMP), a bioactive milk peptide, has therapeutic value in experimental models of skin hypersensitivity, anaphylaxis, and asthma, as it prevents an excessive T helper type 2 cell immune response. The aim of this study was to analyze the effect of GMP on key elements directly involved in the development or control of allergy, in order to improve the precise knowledge about its mechanism of action. METHODS: Rats were systemically sensitized with ovalbumin and orally treated with GMP. Levels of Lactobacillus, Bifidobacterium, and Bacteroides were analyzed in their feces. Splenocytes were isolated and the production of transforming growth factor (TGF)-ß by allergens was measured. Intradermal skin reactions were developed to evaluate in vivo activation of mast cells. Peritoneal mast cells were isolated and activated by the allergen, and histamine secretion was determined. RESULTS: GMP administration increased the amount of intestinal Lactobacillus and Bifidobacterium of allergen-sensitized animals after 3 days of treatment. The increase in Bacteroides was also significant, but only after 17 days of GMP administration. Ten days after treatment cessation, Lactobacillus and Bacteroides were still elevated. GMP intake also elevated the production of TGF-ß in the splenocytes of sensitized animals. In addition, treatment with GMP attenuated mast cell activation by the allergen and inhibited histamine secretion, without affecting the number of mast cells. CONCLUSIONS: The prebiotic action of GMP on allergy-protective microbiota, an increase in TGF-ß production, and a reduction in mast cell response to allergens are novel mechanisms that explain the antiallergic activity of GMP.

Mast cells respond to urticating extract from lepidoptera larva Morpheis ehrenbergii in the rat.

Mast cells and histamine participate in toxic effects of hairs from some caterpillars. This study reports that a crude extract of Morpheis ehrenbergii caterpillar hairs induces in vitro mast cells activation, triggers the release of histamine and causes a rapid urticarial reaction in the rat skin. Heating of the extract abolishes the inflammatory reaction. These results suggest that the use of antihistamines may improve the adverse skin reactions caused by the Mexican caterpillar M. ehrenbergii.

A highly sensitive sandwich ELISA for the determination of glycomacropeptide to detect liquid whey in raw milk.

Milk processing industries and distributors have problems with adulteration of liquid milk by the addition of bovine cheese whey. Recently, the detection of fraudulent manipulation of milk with whey has focused on the identification of glycomacropeptide (GMP). Current non-immunological methods to detect GMP in dairy products are expensive and time-consuming or have low sensitivity. In this study, a novel sandwich enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of whey in raw milk was developed, using a polyclonal rabbit anti-GMP antibody. Calibration curves were constructed by analyzing raw milk standards containing different known concentrations of liquid cheese whey (0.02-20%). The method had a detection limit of 0.047% (v/v) and a quantification limit of 0.14% (v/v). The antibody showed high specificity and no cross-reaction with milk components (other than κ-casein) and was successful in detecting GMP in dairy commercial products. The recovery ratio was between 95.62% and 113.88% for all matrices tested. The intra-assay and interassay coefficients of variation were <6% and <7%, respectively. Finally, it can be stored for 3 months in the form of a ready-to-use kit, while maintaining its accuracy and reproducibility.

[C-reactive protein and interleukin-6 serum levels increase as Chagas disease progresses towards cardiac failure]. / Las concentraciones séricas de interleucina-6 y proteína C reactiva se incrementan a medida que la enfermedad de Chagas evoluciona hacia el deterioro de la función cardíaca.

INTRODUCTION AND OBJECTIVES: Chagas disease is the most common cause of myocarditis in Latin America, including Venezuela. Some 25% of patients progress to chronic chagasic cardiomyopathy, which is characterized by heart failure and arrhythmias. The serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have prognostic value in non-chagasic cardiopathy. The goal of this study was to investigate the relationship between the serum levels of CRP and IL-6 and the developmental stage of Chagas disease. PATIENTS AND METHOD: The study included 64 Chagas disease patients (34 female and 30 male; age 62.2 [1.7] years) and 20 healthy individuals (10 of each sex; age 50.4 [2.7] years). Clinical investigations included echocardiography and measurement of CRP and IL-6 serum levels using ELISAs. Chagas disease patients were graded according to Carrasco et al 1994 classification. Patients with ischemic cardiopathy, liver disease, autoimmune disease, a systemic inflammatory condition, immunosuppression, cancer, pericarditis, or endocarditis were excluded. RESULTS: Multiple regression analysis demonstrated an association between Chagas disease developmental stage and the serum IL-6 level. The serum CRP level increased during only the most advanced phase of the disease. In addition, a high left ventricular mass index was associated with a high IL-6 level and male sex. CONCLUSIONS: IL-6 and CRP serum levels could be of prognostic value in assessing Chagas disease progression because there are significant correlations between elevated levels and the deterioration of cardiac function.

Las concentraciones séricas de interleucina-6 y proteína C reactiva se incrementan a medida que la enfermedad de Chagas evoluciona hacia el deterioro de la función cardíaca / C-reactive protein and interleukin-6 serum levels increase as Chagas disease progresses towards cardiac failure

Introducción y objetivos. La enfermedad de Chagas (EC) es la causa de miocarditis más común en América Latina y Venezuela. El 25% de los pacientes evoluciona hacia una miocardiopatía chagásica crónica (MCC), caracterizada por insuficiencia cardíaca y arritmias. La proteína C reactiva (PCR) y la interleucina-6 (IL-6) tienen valor pronóstico en las cardiopatías no chagásicas. En este estudio se ha determinado la relación entre las concentraciones de PCR e IL-6 y la fase evolutiva de la EC. Pacientes y método. Se incluyó a 64 pacientes con EC (34 mujeres y 30 varones; edad: 62,2 ± 1,7 años) y a 20 individuos sanos (10 de cada sexo; edad: 50,4 ± 2,7 años); en todos ellos se realizaron una valoración clínica, una ecocardiografía y la determinación de las concentraciones séricas de PCR e IL-6 mediante ELISA. Los pacientes fueron clasificados según Carrasco et al (1994). Se excluyó a los pacientes con cardiopatía isquémica, hepatopatías, enfermedades autoinmunitarias, procesos inflamatorios, neoplasias, inmunodepresión, pericarditis y endocarditis. Resultados. El análisis de regresión múltiple mostró una asociación entre la fase evolutiva de la EC y las concentraciones de IL-6, mientras que los valores elevados de PCR sólo estuvieron asociados con la fase más avanzada de la EC. Adicionalmente, se observó un mayor índice de masa del ventrículo izquierdo asociado con valores elevados de IL-6 y el sexo masculino. Conclusiones. Los valores de IL-6 están correlacionadas con la fase evolutiva y los de PCR con las formas más graves de la EC; ambos podrían ser considerados marcadores pronósticos de la MCC

Introduction and objectives. Chagas disease is the most common cause of myocarditis in Latin America, including Venezuela. Some 25% of patients progress to chronic chagasic cardiomyopathy, which is characterized by heart failure and arrhythmias. The serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have prognostic value in non-chagasic cardiopathy. The goal of this study was to investigate the relationship between the serum levels of CRP and IL-6 and the developmental stage of Chagas disease. Patients and method. The study included 64 Chagas disease patients (34 female and 30 male; age 62.2 [1.7] years) and 20 healthy individuals (10 of each sex; age 50.4 [2.7] years). Clinical investigations included echocardiography and measurement of CRP and IL-6 serum levels using ELISAs. Chagas disease patients were graded according to Carrasco et al 1994 classification. Patients with ischemic cardiopathy, liver disease, autoimmune disease, a systemic inflammatory condition, immunosuppression, cancer, pericarditis, or endocarditis were excluded. Results. Multiple regression analysis demonstrated an association between Chagas disease developmental stage and the serum IL-6 level. The serum CRP level increased during only the most advanced phase of the disease. In addition, a high left ventricular mass index was associated with a high IL-6 level and male sex. Conclusions. IL-6 and CRP serum levels could be of prognostic value in assessing Chagas disease progression because there are significant correlations between elevated levels and the deterioration of cardiac function