H1N1 (swine) flu, with more nearly 22,000 confirmed cases worldwide as of June 5, and with 125 deaths globally, including at least 103 blamed on it in Mexico, its place of origin, remains high on the World Health Organization's radar screen.
As a category 5 alert, this new flu strain - an easily spread hybrid of bird, human and flu viruses - is one step shy of sounding the WHO's full pandemic alert siren.
(In the U.S. as of June 5, the CDC had confirmed 13,217 cases of H1N1, which was present in all 50 states, Washington, DC and Puerto Rico, and had caused 27 deaths among various ages.)
Most of the deaths in Mexico, however, "were reportedly adults aged 20 to 49 with no known complicating factors," said Irena Kenneley, PhD, APRN-BC, CIC, a member of the Scientific Research Council of the Association for Professionals in Infection Control and Epidemiology.
So many deaths among the young and seemingly healthy, who usually fend off flu far better than infants or the elderly, has experts speculating that H1N1's lethal mechanism may be the so-called "cytokine storm."
Usually seen in ICU patients battling severe sepsis, the cytokine storm occurs when the body mounts a hyper-reactive immune response so massive it harms itself, sometimes fatally.
It's the biological equivalent of friendly fire.
Immune System Overdrive
Because they have stronger immune systems than the elderly or infants, young adults "could be most poised to produce a cytokine storm," said Kathleen Sullivan, MD, PhD, chief of the Division of Allergy and Immunology at The Children's Hospital of Philadelphia.
The cytokine storm "refers to a state where all guns are firing in a non-organ-specific fashion," she said. "Instead of appropriately directing the immune system to a given target, the process goes into overdrive. When the immune system is attacking on all fronts, it is deleterious."
Cytokines "are chemical messengers produced by white blood cells and tissue cells that regulate the inflammatory response and immunity," said Kenneley, who is an assistant professor at Case Western Reserve University Frances Payne Bolton School of Nursing in Cleveland.
"A cytokine storm occurs when the body's immune system overreacts to an intruder, such as a virus, by producing high levels of cytokines," Kenneley explained. "When too many cytokines are produced, they can stimulate an inflammatory response in which the accumulation of immune cells and fluid at the site of infection may prevent affected tissues and organs such as the lungs from functioning properly and may even cause death due to severe damage and fluid buildup in the lungs themselves."
The relative youth of swine flu casualties bears a disquieting similarity to deaths from the infamous 1918 influenza A H1N1 pandemic. Nearly half of those approximately 50 million casualties were young adults 20 to 40 years old, Kenneley said; although we still don't know what factors may have fueled the 1918 pandemic's engine of death.
In an article published online March 10 in the Journal of Leukocyte Biology, Sullivan and colleagues demonstrated swine flu patients may indeed be at risk of a paralyzed immune system, leading to potentially fatal secondary infections - but for a different reason than the cytokine storm.
Sullivan et al. recruited pediatric patients with severe influenza and compared their pathology with that of five patients with moderate influenza, six with respiratory syncytial virus, and 24 with no health problems who served as controls.
They found elevated levels of cytokines in the severe influenza group, but also a depressed response to toll-like receptor (TLR) ligands, which activate the body's immune cell responses so it attacks invading microbes. Aberrant responses to TLR ligands "may underlie the known susceptibility of influenza-infected patients to secondary bacterial infections," the researchers concluded.
Reactions to her finding so far "have ranged from pleased to surprised," Sullivan told ADVANCE.
The study by Sullivan et al. "brings us a step closer to understanding exactly what goes wrong in some people who get swine flu, so, ultimately, physicians can develop more effective treatment strategies," John Wherry, PhD, deputy editor of the Journal of Leukocyte Biology, told Reuters.
Michael Gibbons is senior associate editor at ADVANCE.