Zusammenfassung
Interleukin (Il)-1β ist der potenteste der bislang beschriebenen physiologischen und pharmakologischen Inhibitoren der Magensäuresekretion der Ratte. Diese Feststellung gilt unabhängig davon, ob die Injektion des Zytokins intra-zerebroventrikulär, -hypothalamisch bzw. -zisternal (0, 01–100 ng) oder intravenös bzw. -peritoneal (0, 1–5, 0 μg) erfolgt. Die niedrigere Potenz von peripher appliziertem Il-1β ist wahrscheinlich durch die überwiegend zentrale Wirkung des über die Blut-Hirn-Schranke transportierten Zytokins bedingt. Periphere Effekte scheinen weniger bedeutsam zu sein. Der säurehemmende zentrale Il-1β Effekt ist lang anhaltend (bis zu 8 h) und wird durch Il-1 Rezeptorantagonisten blockiert. Il-1β interagiert mit spezifischen Rezeptoren in definierten hypothalamischen Kerngebieten und im Hirnstamm, durch die der säurehemmende Effekt induziert wird. Anschließend wird er über nachgeordnete zentrale und periphere PGE2-abhängige Mechanismen vermittelt. Hierbei spielen Somatostatin, Corticotropin releasing factor und adrenerge Mechanismen keine Rolle. Nach zentraler wie nach peripherer Applikation ist I;-1α deutlich weniger effektiv als Il-1β, während Il-4, Il-6 und Tumor Nekrosefaktor α zentral und peripher keinen Effekt auf die Säureskretion in vivo haben. Die Säureproduktion in vitro (isolierte Drüsenschläuche, Parietalzellen) wird durch Il-1α, Il-1β und TNFα nicht beeimiußt. Bei Ratten steigert intrazisternales Il-1β die Serumgastrinspiegel, intraperitoneales TNFα die Peptid-YY-Freisetzung ins portalvenöse Blut, Il-1α die von Gastrin. Diese In-vivo-Effekte auf Gastrin könnten gegenregulatorisch durch die Säurehemmung bedingt sein. Dagegen stellt die Stimulation der Gastrinsekretion von Primärkulturen antraler G-Zellen des Kaninchens wahrscheinlich einen direkten Effekt von Il-1β und TNF-α (0, 01–10 ng/ml) auf diesen Zelltyp dar. Die Säurehemmung durch zentral wirkendes Il-1β ist physiologisch wahrscheinlich nicht relevant. Gastroprotektive Effekte von zentralem Il-1β weisen jedoch auf eine mögliche pathophysiologische Relevanz z.B. bei septischen Zuständen oder Streβ hin. Hier könnte die zentralnervöse Freisetzung von Il-1β durch Hemmung der Säuresekretion blutende Magenschleimhautläsionen verhindern.
Summary
Interleukin (Il)-1β is more potent than any other known physiological or pharmacological inhibitor of gastric acid secretion in the rat. This holds for intracerebroventricular, -hypothalamic or -cisternal (0.01–100 ng) as well as for intravenous or -peritoneal (0.1–5.0μg) application of the cytokine. The lower potency of peripherally administered Il-1β is probably due to the mainly central mode of action of the cytokine after being transported across the blood-brain barrier. Peripheral effects appear to be of minor importance. The antisecretory effect of central Il-1β lasts for up to 8 hours and is blocked by Il-1 receptor antagonists. Il-1β interacts with specific receptors in defined areas in the hypothalamus, brainstem and medulla to induce inhibition of gastric acid secretion. Consecutively, the antisecretory effect is mediated by central and peripheral mechanisms involving the production of PGE2, but not somatostatin, corticotropin-releasing factor and adrenergic mechanisms. Centrally as well as peripherally administered Il-1α are clearly less effective than Il-1β while central and peripheral Il-4, Il-6 and tumor necrosis factor α lack any effect on acid secretion in vivo. Acid production in vitro (isolated glands, parietal cells) is not modulated by Il-1α, Il-1β and TNFα. In rats, intracisternal Il-1β increases the serum gastrin-level while TNFα and Il-1α stimulate the release into the portalvenous blood of peptide YY and gastrin, respectively. These in vivo-effects on gastrin may counterbalance acid inhibition. On the other hand, stimulation of gastrin release from primary cultures of rabbit antral G-cells probably reflects a direct effect on this cell type of Il-1β and TNF-α (0.01–10 ng/ml). In all likelyhood, acid inhibition by central Il-1β is physiologically not relevant. However, gastroprotection by central Il-1β suggests pathophysiological relevance e.g. in septic conditions or stress, where centrally released Il-1β might inhibit acid secretion thereby conferring protection against hemorrhagic lesions of the gastric mucosa.
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Schepp, W. (1995). Exokrine und endokrine Funktionen des Magens. In: Beger, H.G., Manns, M.P., Greten, H. (eds) Molekularbiologische Grundlagen der Gastroenterologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79782-8_14
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DOI: https://doi.org/10.1007/978-3-642-79782-8_14
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