Hyper inflammation and inflammaging: the real connection

Inflammation is a complex body response to harmful pathogens like bacteria and viruses. This can be either short-lived (acute) or long-lasting (chronic), and it involves our defence system, such as white blood cells, cytokines, and phagocytes. They stimulate the release of pro-inflammatory mediators such as interleukins, TNF-α, NF-κβ, prostaglandins, and nitric oxide.

An excessive or uncontrolled amount of these mediators is what we call hyper inflammation syndrome. This condition manifests as persistent fever, low blood cells, organ enlargement, chronic inflammation, bleeding disorder, and multiorgan failure or death in severe cases.

Hyper inflammation is related to major diseases, including Covid-19

Hyper inflammation is often associated with specific diseases and conditions. These include juvenile idiopathic arthritis, systemic lupus erythematosus, Kawasaki disease, and recently, Covid-19. Hyperinflammatory state in Covid-19 is elicited due to an unbalanced immune response. This condition plays a significant causative role in the event of acute respiratory distress syndrome (ARDS) of Covid-19 patients.

Several investigations proved that elevated clinical inflammatory markers and increased serum cytokine and chemokine levels result in the need for mechanical ventilation, development of acute respiratory distress syndrome (ARDS) and Covid-19 related death. Post-mortem investigations also found the infiltration of lymphocytes and macrophages in the lungs, indicating that the severity of Covid-19 is likely more driven by inflammation rather than the viral infection itself.

Inflammaging, immunosenescence, and their connection to hyper inflammation

Effects similar to hyper inflammation are also shown in inflammaging and immunosenescence. Inflammaging is a state of low-grade chronic inflammation that develops alongside ageing. This mechanism can induce age-related diseases and increase morbidity and mortality.

Besides, immunosenescence is the phenomenon of progressive deterioration of the immune system. This deterioration leads to decreased immunity against pathogens and foreign organisms, thus skyrocketing the probability of infections, neoplasia, and autoimmune diseases. Both immunosenescence and inflammaging can happen simultaneously in older people. In advanced age, adaptive immune declines while inflammaging occurs due to the activation of the innate immune system.

Medicinal mushrooms as the source of anti-inflammatory compounds

Mushrooms have been used for medicinal purposes since 3000 B.C. Many investigations in mushrooms have revealed their ability as antiviral, anticancer, antibacterial, and anti-inflammatory agents. It is scientifically proven that medicinal mushrooms contain many beneficial compounds that help inflammation, such as:

  • polysaccharides like Beta-glucans (main active in medicinal mushrooms)
  •  terpenoids like ganoderic acids (Ganoderma lucidum)
  • peptides
  • polyphenols

These bioactive compounds exert specific effects to modulate inflammatory mediators, such as nitric oxide, cytokines, and prostaglandins.

Ganoderma lucidum (Reishi) is the king of the antiinflammatory medicinal mushrooms. In fact, it is described in the literature as showing strong anti-inflammatory actions, mainly because of its high content in terpenoids.

Mushroom terpenoids with anti-inflammatory properties have also been reported in crude extracts of Ganoderma lucidum and Inonotus obliquus. Their tripertene extract remarkably decreased the secretions of TNF-α, IL-6, nitric oxide, prostaglandin and suppressed the activation of NF-κβ luciferase, which are related to hyper inflammation.

In addition, other medicinal mushrooms can also help in inflammation and hyper inflammation. For example, polysaccharides extracted from Agaricus blazei are very promising as an anti-inflammatory agent. A study of extracted polysaccharides that targets pro-inflammatory molecules showed that polysaccharides could inhibit the release of prostaglandin, leukotriene, and the phosphorylation of the serine/threonine. Another polysaccharide extraction from Grifola frondosa also suggested that this biochemical substance could significantly reduce pro-inflammatory cytokines and calprotectin, a marker for inflammation.

Peptides also work against inflammation as reported in a study in which peptides from Cordyceps sinensis and Cordyceps militaris blocked the penetration of inflammation compounds, such as polymorphonuclears cells, IL-1β, and TNF-α. Peptides can also work as neuroprotective agents, protecting the brain from underlying inflammation.

Lastly, polyphenols, which are present in medicinal mushrooms, have been studied for their use in managing inflammation. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression while their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties.


Medicinal mushrooms have been studied intensively for decades for their nutritional and medicinal value. The bioactive compounds in mushrooms such as polysaccharides, terpenoids, peptides, and phenolics can be highlighted as an adjuvant source of anti-inflammatory agents. Therefore, we can benefit from medicinal mushrooms to protect our body from a hyper inflammation state, including inflammaging and immunosenescence.