Lab study supports idea of ‘cytokine storm’ in H5N1 flu

first_img See also: Nov 16, 2005 (CIDRAP News) – A recent laboratory study has produced more evidence that infection of human lung cells with the H5N1 avian influenza virus leads to intense inflammation similar to what was seen in victims of the 1918 Spanish flu pandemic. The H5N1 viruses were “more potent inducers” of cytokines and chemokines—chemical messengers that trigger inflammation—than H1N1 viruses were, says the report by a team led by J.S.M. Peiris of the University of Hong Kong. A flood of inflammation-triggering chemicals released by the immune systems has been referred to as a “cytokine storm.” Autopsies of H5N1 avian flu victims in Vietnam and elsewhere have revealed lungs choked with debris from the excessive inflammation triggered by the virus. Similar severe lung damage was frequently reported in victims of the 1918 pandemic, which disproportionately killed people with the strongest immune systems—young, healthy adults. The Hong Kong researchers sought to test their hypothesis that the H5N1 virus’s ability to trigger a flood of cytokines may contribute to the unusually severe disease it causes in humans. They used H5N1 viruses isolated from a patient who died of the infection in Hong Kong in 1997 and from two Vietnamese patients who were infected in 2004, plus an ordinary H1N1 virus isolated in Hong Kong in 1998. Chan MCW, Cheung CY, Chui WH, et al. Proinflamatory cytokine responses induced by influenza A(H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir Res 2005 (published online Nov 11) [Abstract] Laboratory cultures of human alveolar cells and bronchial epithelial cells were exposed to these viruses. Using real-time polymerase chain reaction (RT-PCR), the researchers assessed the levels of various cytokines and chemokines at several time intervals after infection. “We have found that infection with H5N1 viruses led to the production of 10 times higher levels of cytokines from human cells than normal human flu viruses,” said Peiris, as quoted Nov 12 in The Standard, a Chinese business newspaper.center_img Researchers from Hong Kong report that lung cells growing in a laboratory responded much more intensely to the H5N1 virus than to an ordinary flu virus, even though the viruses reproduced at about the same rate, according to the report published online by Respiratory Research. They found that all the H5N1 viruses caused cells to secrete significantly higher levels of IP-10 (interferon-gamma-inducible protein 10), interferon beta, a type of T cell known as RANTES, and interleukin-6 than the H1N1 virus did. In addition, the 2004 versions of H5N1 caused cells to release more IP-10 at 6 hours than the 1997 version did. Oct 11 CIDRAP News story “Experts cite differences between H5N1 and ordinary flu” The different cytokine responses are not explained by different viral growth rates, because all three virus subtypes replicated with similar efficiency, the article says. “The cellular mechanisms underlying this differential cytokine hyper-induction by H5N1 viruses are presently poorly understood,” it states. The report says previous research has shown that patients with H5N1 disease have higher levels of IP-10 and other chemokines in their blood than do people infected with ordinary flu, a finding that parallels the present laboratory findings. In addition, the article says that studies of recombinant flu viruses carrying genes from the 1918 pandemic virus showed that the recombinant viruses were highly lethal and induced high levels of macrophage-derived chemokines in mice. However, it is not yet clear whether the increased chemokine levels were due to “hyper-induction” of the chemokines or just rapid growth of the virus.last_img read more

No pre-season trip for Benteke

first_img That means he is still waiting to have his medical, scheduled to be held in the UK, and therefore makes flying him halfway around the world to join up with his prospective new team-mates a fruitless exercise. Manager Brendan Rodgers made Benteke his primary summer target to strengthen his forward line but, after initially refusing to meet the buy-out clause, the sale of Raheem Sterling to Manchester City in a £49million deal prompted a shift in thinking. England international Daniel Sturridge made just 18 appearances last season after missing virtually the first five months of the campaign with injury, and is likely to be sidelined until at least September after undergoing surgery on a hip problem, so Rodgers wants a striker who can stand up to the rigours of the Barclays Premier League. He has Benteke’s fellow international Divock Origi, playing his first season in English football after spending last term on loan at Lille, and summer signing from Burnley Danny Ings at his disposal – having decided Mario Balotelli, Rickie Lambert and Fabio Borini are all surplus to requirements – but needed some proven firepower. The club have invested heavily in Hoffenheim’s Brazil international Roberto Firmino, who could cost them up to £29million, but he is not an out-and-out forward and so Rodgers needed to recruit someone else to play as his spearhead. Liverpool have already bought six new players, including England right-back Nathaniel Clyne at a cost of £12.5million, and Benteke’s arrival would push their summer spending to around £80million. Striker Christian Benteke is highly unlikely to join up with Liverpool for any part of their pre-season tour as negotiations continue over his move from Aston Villa. The Reds travel to Adelaide on Saturday for their third match of pre-season preparations and, with no agreement over the finer details of the Belgium international’s transfer, there is little prospect of him flying out in time to make Friday’s game in Malaysia. Liverpool triggered the 24-year-old’s £32.5million release clause on Friday, but Press Association Sport understands negotiations are continuing as the clubs try to reach an arrangement over payment terms. center_img Press Associationlast_img read more