Die Rolle von Vitamin D bei entzündlichen Erkrankungen

Zusammenfassung

Neben skelettalen Endokrinen Effekten gewinnen nichtskelettale Vitamin D3-Wirkungen bei chronischen Erkrankungen, wie denen des Immunsystems, gewinnen an Bedeutung. 1α-Hydroxylase (CYP27B1) und der Vitamin-D-Rezeptor (VDR) wurden in diversen Immunzellen nachgewiesen. Diese Zellen haben damit die Fähigkeit zur Konversion von 25-(OH)-Vitamin-D3 zu 1,25-(OH)₂-Vitamin-D3, das lokal autokrin wirkt. Darüber erfolgt am Immunsystem eine Immunmodulation, die zu einer Verstärkung der angeborenen Immunität mit Stärkung der antibakteriellen Wirkung sowie einer vielfältigen Regulation der erworbenen Immunantwort führt. Vitamin-D-Mangel wird mit der Entwicklung verschiedener Autoimmunerkrankungen, z. B., Diabetes mellitus Typ I, multiple Sklerose, rheumatoide Arthritis (RA), systemischer Lupus erythematodes (SLE), in Verbindung gebracht. Dies gewinnt angesichts des Nachweises einer unzureichenden Vitamin-D-Versorgung in der ganzen Welt an Bedeutung. Bei fast allen rheumatologischen Erkrankungen, wie RA, SLE, systemische Sklerose, ankylosierende Spondylitis sowie M. Behçet, finden sich teils sehr niedrige 25-(OH)-Vitamin D3-Serumspiegel. Bei diesen Erkrankungen lässt sich eine inverse Beziehung zwischen dem 25-(OH)-Vitamin D3-Serumspiegel und der Krankheitsaktivität nachweisen. Bislang ist unklar, ob die hohe Krankheitsaktivität den niedrigen 25-(OH)-Vitamin D3-Serumspiegel bedingt oder umgekehrt. Es lässt sich nicht sicher belegen, dass eine ungünstige Vitamin-D-Versorgung die Inzidenz von RA oder SLE erhöht. Angesichts der immunmodulatorischen Wirkung liegt es nahe, Vitamin D3 als Komedikation in der Behandlung der Autoimmunerkrankungen einzusetzen. Die Ergebnisse teils offener, teils randomisierter Studien (RCT) zeigen bislang keine sicher überzeugenden Wirkungen. Weitere RCT, die sich am individuellen 25-(OH)-Vitamin D3-Serumspiegel ausrichten, höhere 25-(OH)-Vitamin D3-Serumspiegel erreichen und länger dauern, sind erforderlich.

Abstract

Over the last decades, non-skeletal effects of vitamin D3 in several chronic diseases, such as immune-mediated diseases, have gained increasing attention. 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) have been found to be expressed by different cell types of the immune system. These cells are thus able to convert 25-(OH)-vitamin D3 to 1,25-(OH)2-vitamin D3, which act locally in an autocrine fashion, without being subject to control by the endocrine system. Consequently, different immunomodulating effects can be exerted through vitamin D3 including strengthening of the innate immune response, with an amplification of antibacterial effects, and also different regulatory effects of the adaptive immune response. A lack of vitamin D is regarded to be associated with the development of different autoimmune diseases such as type I diabetes mellitus, multiple sclerosis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This is of importance considering the growing evidence of an insufficient alimentary supply of vitamin D world-wide. Low and even very low 25-(OH)-vitamin D3 levels can be found in almost all rheumatic diseases including RA, SLE, systemic sclerosis, ankylosing spondylitis and Behçet’s disease. In all of these diseases an inverse correlation between 25-(OH)-vitamin D3 levels and disease activity can be found. Until now, the underlying cause of this inverse correlation is unclear. Whether high disease activity induces low 25-(OH)-vitamin D3 levels or vice versa remains to be clarified. So far it is not proven that an insufficient supply of vitamin D increases the incidence of RA or SLE. However, considering the immunomodulatory effects of vitamin D on the cells of the immune system, the use of vitamin D3 as a combination partner in the immunosuppressive treatment of autoimmune diseases would be conceivable. Yet, the results of some open-label studies and few randomised controlled trials (RCT) have not revealed any convincing effect so far. Nevertheless, it cannot be excluded that the vitamin D3 dosages and the duration of the trials, both of which were based on the endocrine effects of vitamin D3, were insufficient to achieve autocrine immunomodulatory efficacy. In order to answer this question further RCT are required which use dosages adjusted to individual 25-(OH)-vitamin D3 serum levels, achieve higher systemic levels of 25-(OH)-Vitamin D3 and are of longer duration.

Schlüsselwörter

Vitamin D - Vitamin-D-Mangel - Immunsystem - Autoimmunerkrankung - Behandlung

Key words

vitamin D - vitamin D deficiency - immune system - autoimmune disease - treatment

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