Background and aims: Pro-inflammatory cytokines are the main mediators of juvenile idiopathic arthritis. Modern therapeutic strategies (biologicals) are therefore geared to block the action of individual profinflammatory cytokines selectively. We investigated the effect of selective cytokine blocking on the equlilibrium of associated inflammatory mediators.
Oligoarticular juvenile idiopathic arthritis (oJIA) is an antigen-driven and lymphocyte-mediated disorder affecting the adaptive immune system. Auto reactive T cells produce pro-inflammatory cytokines as IFN-γ and IL-17. Failure of regulatory T cells leads to decreased production of anti-inflammatory IL-10 and results in the loss of immune tolerance. Therapeutic strategies suppress T cell dependent immune responses and consequently inhibit the process of inflammation. The aim of the study was to investigate the effect of T cell suppression on the cytokine network in oJIA patients. Therefore we examined the cytokine concentration after in vitro inhibition of T cells by cyclosporine and abatacept in patients with persistent oJIA and healthy control subjects. This single center cohort study consisted of oJIA affected children and control subjects. Cytokine profiles from cell culture supernatants were examined with multiplex fluorescent bead immunoassay by flow cytometry. High amounts of IL-17 were only observed in the collective of oJIA patients after T cell stimulation. Cyclosporine suppresses its concentration effectively. IL-2 and IFN-γ are present in both groups. We found IL-6 and TNF-α in high concentrations after T cell activation. While TNF-α concentration is suppressed by both drugs, IL-6 concentration remains high in oJIA patients. Concentrations of IL-4 and IL-10 were not found to be influenced in status of activation or suppression. In conclusion, the results of the present study imply that IL-17 is the crucial T cell cytokine in oligoarticular JIA. Only cyclosporine could inhibit the secretion of IL-17 effectively. IL-2 and IFN-γ are not specific for oligoarticular JIA. Both cytokines are found as well in healthy control subjects after T cell stimulation. Relevant pro-inflammatory macrophage cytokines in oli-* Corresponding author. L. Strothmann et al.134 goarticular JIA are TNF-α and IL-6. T cell suppression by cyclosporine and abatacept inhibits TNF-α but not IL-6 effectively. Production of anti-inflammatory cytokines is not influenced by T cell suppression.
Oligoarticular juvenile idiopathic arthritis (oJIA) is an antigen-driven and lymphocyte-mediated autoimmune disorder with irregularity in the adaptive immune system. Auto reactive T cells, activated by cartilage-derived auto antigens, produce pro-inflammatory cytokines as IFN-γ and IL-17. Failure of regulatory T cells leads to decreased anti-inflammatory cytokine IL-10 production and results in the loss of immune tolerance. This activation of innate and adaptive immunity stimulates the release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α. Thus, inhibition of these cytokines is considered as an appropriate therapeutic strategy for oJIA. The aim of this study was to investigate whether the blockade of a single cytokine pathway in the present cytokine setting causes an unfavourable imbalance in the cytokine system or whether the blockade is sufficient to suppress the inflammatory condition. We examined the cytokine secretion after in vitro inhibition of IL-1 and TNF-α of patients with oJIA and healthy subjects. This single center cohort study consisted of oJIA affected children and control subjects. Cytokine profiles from cell culture supernatants were examined with multiplex fluorescent bead immunoassay by flow cytometry. Adalimumab prevents highly effective and very selective effect of the cytokine TNF-α. Due to its structure, the mode of action of etanercept is difficult to display. In addition, adalimumab and etanercept appear in vitro suppressive to IFN-γ. The efficiency of both substances is particularly supported by the increased secretion of anti-inflammatory cytokine IL-4. In contrast, anakinra unselectively inhibits the pro-inflammatory macrophage cytokines. To conclude, our observations suggest that inhibition of IL-1 or TNF-α may contribute to the unselective decline of other pro-inflammatory cytokines in oJIA patients. The selective anti-inflammatory effect of cytokine inhibitors is most * Corresponding author. M. Kirchner et al. 111likely supported by an increase of IL-4 or IL-10. It still remains to be elucidated whether the reduced IFN-γ secretion is maybe causative for the increased susceptibility to infections with opportunistic pathogens.
ZusammenfassungEinleitung: 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.