Zusammenfassung
Entzündungen bekämpfen Pathogene nach Verletzungen und chirurgischen Eingriffen. Durch
die Entzündungsreaktion wird das Muskel- und Fettgewebe katabolisiert, damit Aminosäuren,
Glukose und Fettsäuren für die Immunantwort freigesetzt werden können. Die Leber erhöht
die Proteinsynthese während der akuten Phase und die antioxidativen Abwehrmechanismen
werden durch vermehrte Glutathionsynthese verstärkt. Die Produktion von Oxidantien
schafft pathogenfeindliche Umweltbedingungen. Entzündungshemmende und -fördernde Zytokine
steuern das Ausmaß der Immunantwort. Zur ersten Kategorie gehören die Interleukine
(IL) 1 und 6 und der Tumornekrosefaktor-α (TNF-α), während IL-10 zur zweiten Kategorie
gehört. Neuroendokrine Reaktionen treten auf und Hitzeschockproteine entstehen zur
Dämpfung der Entzündungsreaktion. Entzündungen können sowohl schädigend als auch tödlich
sein. Eine hohe Produktion von IL-1 und TNF-α erhöht die Sterblichkeit bei zerebraler
Malaria, Meningitis und Sepsis. Das Verhältnis der entzündungsfördernden zu den entzündungshemmenden
Proteinen kann ebenfalls einen ungünstigen Verlauf einer Infektion bewirken. Ein hohes
IL-6/IL-10- oder IL-10/TNF-Verhältnis kann eine erhöhte Sterblichkeitsrate bewirken,
während IL-1, IL-6 und TNF-α ebenfalls schädigende Auswirkungen bei Entzündungen und
bei der Entwicklung atheromatöser Beete haben. Der Genotyp ist ein Schlüsselfaktor
bei der Beeinflussung der Zytokinenproduktion und der Stärke der Entzündungsreaktion.
Die Produktion von TNF-α, IL-1β, IL-6 und IL-10 wird stark beeinflusst vom Polymorphismus
einzelner Nukleotide (SNPs) in der Promoterregion der entsprechenden Gene. Zytokin-Gen-Allele
bewirken bei einigen Erkrankungen und Zuständen eine erhöhte Morbidität einschließlich
Sepsis, Diabetes mellitus und kardiovaskuläre Erkrankungen. Studien hinsichtlich der
antientzündlichen Wirkung von n-3-PUFAs deuten darauf hin, dass der individuelle Genotyp
die Wirksamkeit der Immunonährstoffe zur Kontrolle einer Entzündung beeinflussen kann.
Zur Besserung des Zustandes der Patienten ist eine bessere Kenntnis des Gebrauchs
der Nährstoffe wie z. B. der n-3-PUFAs zur Kontrolle entzündlicher Vorgänge erforderlich
und ein besseres Verständnis des Einflusses des individuellen Genotyps auf die Anwort
des Organismus auf solche Immunonährstoffe.
Abstract
The function of inflammation is to combat pathogens following injury and surgery.
During the inflammatory response, muscle and adipose tissue are catabolised to provide
amino acids, glucose and fatty acids, for the immune response. The liver increases
acute phase protein synthesis and anti-oxidant defences are enhanced by increased
glutathione synthesis. Oxidants production creates a hostile environment for pathogens.
The strength of the response is modulated by pro-inflammatory and anti-inflammatory
cytokines. Interleukins (IL) 1 and 6 and tumour necrosis factor-α (TNF-α), fall into
the first category, and IL-10 into the second. Neuroendocrine responses occur, and
heat shock proteins are produced to curtail the inflammatory response. Inflammation
exerts damaging and lethal effects. High production of IL-1 and TNF-α increases mortality
in cerebral malaria, meningitis and sepsis. The ratio of pro- to anti-inflammatory
cytokines also result in an adverse outcome to infection. High IL-6 to IL-10, and
IL-10 to TNF ratios are associated with raised mortality. IL-1, IL-6 and TNF-α also
play a damaging role in inflammatory disease and atheromatous plaque development.
Genotype is a key factor which influences cytokine production and the strength of
the inflammatory response. TNF-α, IL-1β, IL-6 and IL-10 production is strongly influenced
by single nucleotide polymorphisms (SNPs) in the promoter region of the respective
genes. Cytokine gene alleles are linked to increased morbidity in a range of diseases
and conditions including sepsis, diabetes mellitus and cardiovascular disease. Studies
on the anti-inflammatory effect of n-3 PUFAs indicate that individual genotype may
influence the efficacy of immunonutrients in controlling inflammation. To improve
patient outcome a better understanding is needed, of how nutrients, such as n-3 PUFAs
can be used to control the inflammatory process and how individual genotype influences
the response to such immunonutrients.
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Robert Francis Grimble
Institute of Human Nutrition · School of Medicine · University of Southampton
SO16 7PX · GB
