In-vitro-Einfluss von Adalimumab und Anakinra auf das Zytokin-netzwerk bei Patienten mit oJIA und sJIA

Zusammenfassung

Einleitung: Die oJIA gilt als Autoimmun-erkrankung der adaptiven Immunität, die sJIA wird als Autoinflammationserkrankung gewertet. Bei beiden Verlaufsformen werden die proinflammatorischen Zytokine IL-1, IL-6 und TNF-α hochreguliert. Daher gilt die Inhibition proinflammatorischer Zytokine als geeignete therapeutische Strategie. Die Autoren untersuchten, welchen Einfluss die Blockade eines einzelnen Zytokins auf das Gleichgewicht des gesamten Zytokinsystems nimmt.

Methoden: Hierzu wurde die Zytokinsekretion nach In-vitro-LPS-Stimulation und Hemmung von IL-1 und TNF-[uni03B1] bei Patienten mit oJIA, sJIA und gesunden Probanden analysiert.

Resultate: Anakinra hemmt unselektiv alle untersuchten proinflammatorischen Zytokine. Adalimumab verhindert sehr selektiv die Wirkung von TNF-α. Adalimumab und Anakinra unterdrücken die Sekretion des antiinflammatorischen IL-10 bei sJIA-Patienten und Gesunden. Beide Biologika supprimieren IFN-γ signifikant. Die Autoren zeigten, dass Biologika nicht nur die Zielzytokine, sondern auch andere Zytokine unselektiv blockieren.

Diskussion: Es bleibt zu klären, ob die reduzierte IFN-γ-Sekretion als Folge der Biologikatherapie der JIA verantwortlich für die erhöhte Infektanfälligkeit gegenüber opportunistischen Erregern ist.

Summary

Introduction: OJIA is an autoimmune disorder with irregularity in the adaptive immune system, while sJIA shows distinct clinical and laboratory features, reflecting systemic inflammation. The activation of immunity stimulates the release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α. Cytokine inhibition is considered as an appropriate therapeutic strategy for JIA.

Methods: We investigated whether the blockade of a single cytokine pathway in the present cytokine setting causes an imbalance in the cytokine system. We examined the cytokine secretion after in vitro inhibition of IL-1 and TNF-α of patients with oJIA, sJIA and healthy subjects. Adalimumab prevents highly effective and very selective the effect of TNF-α. Adalimumab and anakinra appear suppressive to IFN-γ. Anakinra unselectively inhibits the pro-inflammatory macrophage cytokines.

Discussion: Our observations suggest that inhibition of IL-1 or TNF-α may contribute to the unselective decline of other pro-inflammatory cytokines in oJIA and sJIA patients. It still remains to be elucidated whether the reduced IFN-γ secretion is maybe causative for the increased susceptibility to infections with opportunistic pathogens.

Schlüsselwörter

Oligoartikuläre juvenile idiopathische Arthritis (oJIA) - systemische juvenile idiopathische Arthritis (sJIA) - pro-/antiinflammatorische Zytokine - Zytokin-Inhibition

Keywords

Oligoarticular juvenile idiopathic arthritis - systemic juvenile idiopathic arthritis - pro-/anti- Inflammatory cytokines - cytokine inhibition

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