Effects of too much inflammation

Inflammation (not to be confused with infection) – when tissues become swollen, hot and often painful – is the body’s normal response to injury or infection and is necessary to kick-start the healing process by allowing plasma and leukocytes to the affected area. But sometimes the body gets it wrong and creates too much inflammation, which can have a dangerous cascading effect causing tissue damage. This, in turn, causes more inflammation, disease and eventually organ failure.

Possible applications of portable bioreactor

Researchers from the University of Pittsburgh in the US have developed a bioreactor (a sort of artificial organ) holding human liver cells that makes and pumps out an anti-inflammatory protein to prevent organ damage and other complications. The authors suggest that the portable device would be useful in battlefield situations where early intervention to control systemic inflammation after injury might improve the chances of survival. It could also be used to help patients fight acute bacterial infections on their own while holding the associated inflammation in check.

The device was effective in reducing acute inflammation caused by bacterial products in rats – they gave the rats sepsis that they were able to treat.

Prevalence of sepsis

Sepsis is an inflammatory disease and a significant public health concern, which, the researchers write, is possibly the 10th leading cause of death overall in the United States, accounting for nearly 10% of total deaths in the US. The death rate of those infected varies between 28–50%. In addition, the rate of sepsis is rising, possibly because of ageing populations, the growth of drug-resistant bacteria and immune-suppressing medical treatments (such as chemotherapy).

Death from sepsis occurs due to inflammation-induced multiple organ dysfunction syndrome (MODS), with sequential and gradual loss of organ function.

“In sepsis ... the inflammatory response evolves almost too quickly but the available treatment strategies aim to prevent inflammation entirely,” lead researcher Dr Yoram Vodovotz said in a press release. “A better approach would be to turn down the response when it’s too strong, yet still have appropriate inflammation signalling to promote tissue repair.”

Bioreactor elevates circulating sTNFR

The researchers loaded their bioreactor device with modified human liver cells that were designed to make soluble tumour necrosis factor-alpha receptor (sTNFR). This receptor is responsible for regulating cytokine tumour necrosis factor-a (TNF-a) – the substance that drives the inflammation process. Generally, people (and rats) suffering from sepsis don’t make enough sTNFR. When the device was rigged up to an intravenous line, blood from an anaesthetised rat suffering from acute inflammation was pumped through the bioreactor using the rat’s own circulation system. The bioreactor successfully elevated circulating sTNFR, reduced the levels of TNF-a and other key inflammatory mediators, alleviated hypotension and reduced circulating markers of organ damage.

Customised treatment possible in the future

Although much more testing on animals and further development of the device is needed, it does hold the very promising opportunity of finally offering an effective treatment to control inflammation. The researchers have also theorised that the device could be loaded with different types of modified cells to produce sTNFR at different rates – allowing customised treatment to be able to harness the beneficial effects of inflammation but to not allow the inflammation to exceed a threshold that becomes self-sustaining and dangerous for the patient.

“Ultimately, therefore, this type of device should produce sTNFR, or any other therapeutic molecule, in a manner that adapts to an individual’s inflammatory dynamics,” the team concluded in their recent paper.

Their research was published in May 2012 in the new science journal Disruptive Science and Technology.