In a new study, researchers found a possible reason for the increased inflammatory state in the elderly, and why the monocyte profile (a type of white blood cell) is altered. The results can also explain why older folks are at an increased risk of contracting pneumonia caused by the bacteria Streptococcus pneumoniae.
The research article, “TNF Drives Monocyte Dysfunction with Age and Results in Impaired Anti-pneumococcal Immunity,” was published in PLOS Pathogens.
It has been known that as we age, the levels of inflammatory cytokines increase in the blood and tissues. While inflammation is an important immune system response, chronic inflammation is connected to many diseases and associated to weaker healthy responses. This constant state of inflammation, also characterized by increased levels of circulating monocytes and sometimes referred to as “inflamm-aging,” is an important contributor to the decline of health status in elderly people.
Research into this topic has also demonstrated that older individuals with increased levels of inflammatory cytokines — levels over the average for their age — are at higher risk of becoming infected, hospitalized, and possibly dying from Streptococcus pneumoniae–caused pneumonia. Despite all this evidence, it still had been unclear how age-associated inflammation increased susceptibility and vulnerability to this pathogen.
In the new study, researchers investigated the role of monocytes in this process. Monocytes are immune cells that mature in the bone marrow and are recruited to the sites of injury or infection; once there, these cells turn into macrophages, which “clean” the body of pathogens, cell waste, and infected cells. Monocytes produce potent pro-inflammatory cytokines, such as TNF and IL-6, and are found to be increased in older people, an observation that still puzzles scientists.
The team studied younger and older mice, and found higher levels of monocytes, both in circulating blood and the bone marrow, in older mice. Furthermore, the inflammatory cytokine TNF was also present in higher levels in elderly mice and older human donors. The scientists observed that the increase of TNF caused the monocytes to leave the bone marrow prematurely and, when stimulated by bacterial products, these immature cells produce even more pro-inflammatory cytokines, further increasing the inflammatory state. Despite this increased inflammation, old mice are not able to clear the penumonia bacteria.
Interestingly, through elimination of TNF — either pharmacologically or genetically, or through a reduction in the levels of monocytes — the scientists were able to restore the antibacterial activity of older mice.
The study demonstrated that monocytes are both influenced and contributors to the high levels of inflammatory cytokines, and that this chronic age-related inflammation increases the susceptibility to the pneumonia-causing S. pneumoniae.
Researchers concluded in their article, “Although it may be counterintuitive to limit inflammatory responses during a bacterial infection, the clinical observations and our animal model indicates that anti-bacterial strategies need to be tailored to the age of the host.”