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

Eleven children with acute encephalopathy associated with an influenza viru s infection were treated during the 1997-1998 influenza season. Reverse tra nscription-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 neu rological complications. Viral RNA was detected only in the peripheral bloo d mononuclear cells of one patient with influenza-virus-associated encephal opathy (1 of 9; 11%) and in the CSF of another patient (1 of 11; 9%). RT-PC R was negative in the blood of all the controls, but the percentage of RT-P CR-positive samples in the two groups was not significantly different. Cyto kines and soluble cytokine receptors in plasma and CSF were then quantified using an enzyme-linked immunosorbent assay. The CSF concentrations of solu ble tumor necrosis factor receptor-1 were elevated in two patients and inte rleukin-6 (IL-6) was elevated in one patient with influenza-virus-associate d encephalopathy. On the other hand, the plasma concentrations of IL-6 were elevated in four of nine patients. The number of encephalopathy patients w ho had elevated plasma concentrations of IL-6 100 pg/ml was significantly h igher than that of controls (P = .01). In conclusion, the infrequent detect ion 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. Proinflam matory cytokines and soluble cytokine receptors may mediate the disease. Th e high plasma concentration of IL-6 could be an indicator of the progressio n to encephalopathy. J. Med. Virol. 58:420-425, 1999. (C) 1999 Wiley-Liss, Inc.