Der Immunmetabolismus umfasst die Wechselwirkungen zwischen Stoffwechselprozessen
und Immunantwort – er spielt damit eine wichtige Rolle bei der Regulation von Entzündungsreaktionen
und hat signifikanten Einfluss auf den Sepsisverlauf. Aber nicht nur die Immunreaktion
beeinflusst die Stoffwechselwege, auch eine Modulation der Stoffwechselwege wirkt
sich wiederum auf die Immunität der zugehörigen Zelle und damit den Zustand des Immunsystems
aus.
Abstract
Immunometabolism is a fascinating field of research that investigates the interactions
between metabolic processes and the immune response. This intricate connection plays
a pivotal role in regulating inflammatory reactions and consequently exerts a significant
impact on the course of sepsis. The proinflammatory response during an immune reaction
is closely tied to a high energy demand in immune cells. As a result, proinflammatory
immune cells rapidly require substantial amounts of energy in the form of ATP, necessitating
a fundamental and swift shift in their metabolism, i.e., their means of generating
energy. This entails a marked increase in glycolysis within the proinflammatory response,
thereby promptly meeting the energy requirements and providing essential metabolic
building blocks for the biosynthesis of macromolecules. Alongside glycolysis, there
is heightened activity in the pentose phosphate pathway (PPP). The PPP significantly
contributes to NADPH production within the cell, thus maintaining redox equilibrium.
Elevated PPP activity consequently leads to an increased NADPH level, resulting in
enhanced production of reactive oxygen species (ROS) and nitric oxide (NO). While
these molecules are crucial for pathogen elimination, an excess can also induce tissue
damage. Simultaneously, there are dual interruptions in the citric acid cycle. In
the cellular resting state, the citric acid cycle acts as a sort of “universal processor”,
where metabolic byproducts of glycolysis, fatty acid breakdown, and amino acid degradation
are initially transformed into NADH and FADH2, subsequently yielding ATP. While the
citric acid cycle and its connected oxidative phosphorylation predominantly generate
energy at rest, it becomes downregulated in the proinflammatory phase of sepsis. The
two interruptions lead to an accumulation of citrate and succinate within cells, reflecting
mitochondrial dysfunction. Additionally, the significantly heightened glycolysis through
fermentation yields lactate, a pivotal metabolite for sepsis diagnosis and prognosis.
Conversely, cells in an anti-inflammatory state revert to a metabolic profile akin
to the resting state: Glycolysis is attenuated, PPP is suppressed, and the citric
acid cycle is reactivated. Of particular interest is that not only does the immune
reaction influence metabolic pathways, but this connection also operates in reverse.
Thus, modulation of metabolic pathways also modulates the immunity of the corresponding
cell and thereby the state of the immune system itself. This could potentially serve
as an intriguing avenue in sepsis therapy.
Schlüsselwörter
Immunmetabolismus - Sepsis - Stoffwechsel - Zitratzyklus - Pentosephosphatweg - Glykolyse
- Proinflammation - Antiinflammation
Keywords
immunometabolism - sepsis - metabolism - citric acid cycle - pentose phosphate pathway
- glycolysis - pro-inflammation - anti-inflammation
