Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy

Abstract

Eleven children with acute encephalopathy associated with an influenza virus infection were treated during the 1997-1998 influenza season. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the viral genome in peripheral blood and cerebrospinal fluid (CSF) samples. The results were compared with those of control influenza patients without neurological complications. Viral RNA was detected only in the peripheral blood mononuclear cells of one patient with influenza-virus-associated encephalopathy (1 of 9; 11%) and in the CSF of another patient (1 of 11;9%). RT-PCR was negative in the blood of all the controls, but the percentage of RT-PCR-positive samples in the two groups was not significantly different. Cytokines and soluble cytokine receptors in plasma and CSF were then quantified using an enzyme-linked immunosorbent assay. The CSF concentrations of soluble tumor necrosis factor receptor-1 were elevated in two patients and interleukin-6 (IL-6) was elevated in one patient with influenza-virus-associated encephalopathy. On the other hand, the plasma concentrations of IL-6 were elevated in four of nine patients. The number of encephalopathy patients who had elevated plasma concentrations of IL-6 100 pg/ml was significantly higher than that of controls (P= .01). In conclusion, the infrequent detection of the viral genome in the CSF and blood showed that direct invasion of the virus into the central nervous system was an uncommon event. Proinflammatory cytokines and soluble cytokine receptors may mediate the disease. The high plasma concentration of IL-6 could be an indicator of the progression to encephalopathy.

Master donor viruses A/Leningrad/134/17/57 (H2N2) and B/USSR/60/69 and derived reassortants used in live attenuated influenza vaccine (LAIV) do not display neurovirulent properties in a mouse model

“…For example, influenza virus or viral antigens are rarely demonstrated in the cerebrospinal fluid or brain of patients suffering from influenza encephalopathy [7,14,19]. In addition, Guillain Barré, Kleine-Levin and Reye's syndrome all are associated with infections not necessarily involving influenza virus, and, in the case of Reye's syndrome, the role of viral infection, if there is any, may be limited [3,17].…”

Prognostic predictive values of serum cytochrome c, cytokines, and other laboratory measurements in acute encephalopathy with multiple organ failure

“…It triggers the execution phase of apoptosis by massive translocation into the cytoplasm, leading to Apaf-1 mediated caspase activation. 10 Our results suggested that apoptosis as well as inflammation [3][4][5][6][7] in vascular vessels was involved in the development of severe encephalopathy. Findings from pathological examination suggest that direct viral invasion and inflammation in CNS are not likely to cause this disease.…”

“…[3][4][5][6][7] Hypercytokinaemia, therefore, is suggested to have an important role in the pathogenesis of acute encephalopathy and multiple organ dysfunction. 9 From the suspected pathogenesis, anti-inflammatory therapies (methylprednisolone pulse therapy, high dose gamma globulin therapy, and plasma exchange therapy) are proposed for the treatment of the illness.…”

Replication of influenza A virus in swine umbilical cord epithelial stem-like cells

“…However, virus infection has been detected in extra-pulmonary tissues. [33][34][35][36] Influenza virus genome and viral antigens were also detected in reproductive organs and fetal tissues and the virus has been associated with causing abortions and fetal abnormalities.…”