Pneumonia is a respiratory disease caused a bacterial or viral infection of the lungs. The condition is characterized by a fever, a cough, chest pain, breathing problems, and mucus production. When a person has pneumonia, the body uses immune cells to kills the pathogens, but the process also damages lung tissue. A team of researchers studying how the immune system combats pneumonia found a way to help immune cells do their job without causing major lung damage.

How the Immune Cells React with Pneumonia

Pneumonia occurs when the lungs become inflamed due to infection or exposure to chemicals. While most cases of pneumonia are bacterial, some are triggered by viruses and fungi. At the physiological level, the immune system is responsible for keeping bacteria from reaching the lungs. The bacteria can come from the others parts of the body, such as the gut area or the skin. If the immune system is busy dealing with another set of invaders, the bacteria can grow out of control and travel to the lungs, resulting in pneumonia.

According to UNICEF, the lung condition remains a leading cause of death among children under five years of age. An estimated 2,400 children die from pneumonia every year. In fact, pneumonia has been accounted for about 880,000 deaths in children under five in 2016. Those deaths could have been avoided using preventive measures, including antibiotics. However, the world is currently engaged in a difficult fight against antimicrobial-resistant bacteria.

Instead of developing another class of antibiotics for pneumonia, researchers at Boston Children's Hospital described an approach to help patients fight the lung condition. The approach involves the strengthening of the immune cells while reducing their adverse effects on lung tissue.

The immune cells the researchers were pertaining to are usually the first responders at the site of a bacterial infection. They are called neutrophils, white blood cells that defend the body by engulfing pathogens. Neutrophils can also release toxic chemicals to kill pathogens in the body. Unfortunately, a large number of neutrophils in the site of infection, such as the lungs, can cause inflammation that damages healthy tissue. This was the problem tackled by the researchers in a recent study.

A Better Way to Combat the Condition

"The question is when we have pneumonia, do we want to enhance neutrophil function or suppress it? It's very tricky," said Dr. Hongbo Luo, the senior author of the study and a researcher in the Department of Laboratory Medicine at Boston Children's Hospital.

With the collaboration at the Chinese Academy of Medical Sciences and Peking Union Medical College in China, Dr. Luo and colleagues discovered the role of the IP6K1 gene neutrophils. The inositol hexakisphosphate kinase 1 is a gene that encodes a protein in the IPK family. But it can be inhibited by another molecule called PIP3 in neutrophils, according to previous studies in Dr. Luo's lab.

If IP6K1 has been inhibited, the PIP3 becomes more expressed in neutrophils that causes them to become more potent in killing bacteria. To determine if disabling the gene can lead to better neutrophils, the researchers used mice models and deleted their IP6K1 gene. They found that white blood cells have been enhanced and became more effective in eliminating the bacterial infection. Moreover, the aggression of neutrophils did not lead to severe lung damage, instead, the lung tissue suffered low impact from the defenders.

"This was a surprise. The exciting thing is that bacterial killing is high, and tissue damage is low," added Dr. Luo.

Upon further investigation about the low tissue damage, the research team identified that blood platelets were regulating neutrophils in action. The platelets produced a chemical called polyphosphate that enhanced the white blood cells, instead of overpopulating them in the infection site.

A closer inspection explained that the inhibition of IP6K1 gene causes platelets to produce less polyphosphate, which led to the fewer number of neutrophils. But the neutrophils gathered by the platelets were more efficient in eliminating bacteria, which resulted in significantly less tissue damage. The researchers also proved that an inhibitor drug called TNP for IP6K1 worked as effectively as genetic manipulation.

The researchers clarified that TNP has never been tested as a potential drug among humans. But their findings may be useful in several infections being dealt by neutrophils. Dr. Luo is planning to pursue further study among cancer patients, who are prone to pneumonia, to determine if inhibition of the gene can help raise their low neutrophil count.

Pneumonia is a life-threatening condition especially in people with a compromised or weakened immune system, such as very young children, patients with cancer, patients with tuberculosis, people with HIV infection, and individuals infected with influenza. Treatment options for the condition include administration of antibiotics, increased intake of fluids, use of cool mist humidifiers, and cough medication.

[메디컬리포트=Ralph Chen 기자]

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