Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 firstdegree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their firstdegree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

Pegylated interferon with ribavirin in the treatment of chronic active hepatitis C in Egyptian patients: efficacy of response in a retrospective study

Chronic hepatitis C is one of the major causes of cirrhosis, hepatocellular carcinoma and considered the main indication for liver transplantation. In Egypt, high HCV rates were reported among several population groups reaching up to 20%. Interferon Alfa is the current therapy forchronic hepatitis C .Yet, combination therapy of Alfa interferon and ribavirin is more effective than interferon alone in increasing the response rates. Aim of work is to study efficacy of response in Egyptian patients with chronic active hepatitis C who had received pegylated interferon plus ribavirin as regarding the biochemical and virologic response. The results of this study showed that patients received Pegylated interferon alfa-2a plus ribavirin had significant improvement in serum ALT levels in around 71% of them. Also 58.94%of these patients achieved sustained clearance of the virus six months after stopping treatment. The combination therapy of Pegylated interferon alfa and ribavirin is effective in achieving biochemical and virological responses and is highly recommended as an initial therapy for patients with chronic hepatitis C

An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever.

Effect of some immunomodulators on the host- parasite systen in experimental hymenolepiasis nana

Mice experimentally infected with H. nana and injected with immunosuppressant [cyclophosphamide [Cp] and lead nitrate [Ln] showed significant increase in infection intensity, significant decrease in intestinal mast cell count, dissemination of larvae to the liver, toxic hepatitis and absence of specific serum IgG. Cyclophosphamide caused morphological abnormalities in adult worms, prolongation of patent period and more severe villous changes. Immuno-stimulants represented by Levamisol [Lv] and gamma interferon [IFN-alpha] caused significant decrease in infection intensity, significant shortening of patent period and early improvement of histopathological changes. Immunostimulants, particularly IFN-alpha, were highly effective in counteracting hyperi nfection seen with immuno-suppression. The study confirmed the deleterious effects of immunosuppression on hymenolepiasis and suggested a beneficial role for immunotherapy for immunosuppressed patients

Effect of interferon: a on experimental schistosoma mansoni infection in mice

To investigate the immunomodulatory effect of the Th1 mediated cytokine IFN-alpha on schistosomiasis, this cytokine was weekly injected into mice experimentally infected with S. mansoni, beginning from day 0 [group II], week 3 [group III], week 6 [group IV] and week 10 [group V] post-infection. TGF beta 1 serum levels were estimated on a weekly basis and beginning one week after initiation of IFN-alpha therapy, while all animals were sacrified on week 14 to be used for egg counts in liver and small intestine, oogram study for determination of the maturity of deposited eggs, and histopathological examination of stained liver sections. IFN-alpha treated groups were characterized by a more intense oviposition in the intestine [liver/intestine ratio less than 1], with higher egg numbers the earlier IFN-alpha was administered. Oograms of the intestine indicated the level of immature eggs to be statistically significantly higher in group II, III and IV than in the control group I [p < 0.05]. In IFN-alpha medicated mice, the mean numbers and diameters of hepatic granulomas were less than in GI, in addition to a lower representation of fibrocellular and fibrous granulomas among them [all parameters p < 0.05], especially in Gs IV and V. The inflammatory cell population in the form of eosinophils, histiocytes and giant cells was more pronounced in Gs III, IV and V. TGF-beta 1 serum levels showed a progressive rise, however more pronounced in the untreated control. A statistically positive significant was established between TGF-beta 1 levels and number, size and percentage of fibrotic hepatic granulomas in all groups

Nuevo tratamiento para la transformación maligna del epitelio, inducida por VPH, en la laringe / New treatment for the malignant transformation of the epithelium, induced by HPV, in larynx

El papel del VPH en la etiología del cáncer de laringe, reconocido por evidencias histológicas, inmunohistoquímicas y particularmente por técnicas de hibridización, que han identificado una doble presencia "activa" y "latente" del virus; quedó demostrado en nuestros cuatro primeros pacientes por el curso atípico, agresivo y destructivo localmente que provocó la muerte en el primer paciente por estallido de la carótida, erosinada por la recurrencia incontrolable de la enfermedad papilomatosa; y en los siguientes tres pacientes, actualmente libres de enfermedad, pero luego de tratamiento radical que incluyó el sacrificio de la laringe. En el quinto paciente, la presencia de atípias coilocíticas que acompañaron a la rápida descompensación de los síntomas en un lapso menor de 6 meses, luego de 20 años de papilomatosis y multiples resecciones, lo interpretamos como la etapa inicial de la transformación maligna del epitelio inducido por el VPH. Entonces, buscando "erradicar" la presencia del VPH y evitar que el curso siga hasta el carcinoma como en los primeros cuatro pacientes, a través de la laringofisura resecamos con bisturí cada una las lesiones papilomatosas, incluyendo en cada una un margen de mucosa sana y, en profundidad hasta la submucosa; electrocoagulamos cada lecho e inyectamos en su centro y periferie por vía submucosa, 1.000.000 UI de Interferon alfa 2-b por lesión resecada, para un total de 12.000.000 UI. A los 9 meses de esta nueva forma de tratamiento, por primera vez practicada, se encuentra asintomático; definitivamente se ha prolongado el tiempo libre de enfermedad y sin evidencia de recurrencia activa del virus