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Expression of IL-8 in Kawasaki disease
1Department of Paediatrics, Nippon Medical School, Tokyo, Japan. Asano_Takeshi/paediatrics@nms.ac.jp
Abstract:
We investigated, by Northern blotting, ELISA, and a chemotaxis assay, the expression of IL-8 mRNA, the production of IL-8 protein, and the biological activity of mononuclear cells (MNC), polymorphonuclear neutrophils (PMN) and plasma, respectively, from patients with Kawasaki disease (KD) who received intravenous immunoglobulin (IVIG). IL-8 mRNA expression by MNC and PMN, the level of IL-8 protein, and the neutrophil chemoattractant activity within plasma were all increased in the acute phase of KD, and were significantly elevated following IVIG therapy. The level of chemotactic activity of neutrophils, but not that of monocytes, in response to F-met-leu-phe was decreased in patients with KD after IVIG. The increased expression of IL-8 in PMN and MNC, the increased plasma level of IL-8 and the decreased level of neutrophil chemotactic activity of the patients who received IVIG therapy might inhibit the accumulation of neutrophils at the sites of inflammation, and may thus reduce the risk of aneurysm formation.
Insights
Kawasaki disease (KD) patients show increased IL-8 in acute phases and after IVIG treatment. This may reduce neutrophil accumulation, potentially lowering aneurysm risk.
Area of Science:
- Immunology
- Molecular Biology
- Pediatric Cardiology
Background:
- Kawasaki disease (KD) is an acute febrile illness affecting young children, characterized by systemic vasculitis.
- Interleukin-8 (IL-8) is a key chemokine involved in neutrophil recruitment and inflammation.
- Intravenous immunoglobulin (IVIG) is the standard treatment for KD, but its precise immunomodulatory mechanisms are still being investigated.
Purpose of the Study:
- To investigate the expression of IL-8 mRNA and protein in patients with Kawasaki disease (KD) during the acute phase and following IVIG treatment.
- To assess the biological activity of IL-8, including its effects on mononuclear cells (MNC), polymorphonuclear neutrophils (PMN), and plasma.
- To explore the potential role of IL-8 modulation in preventing coronary artery aneurysm formation in KD patients.
Main Methods:
- Northern blotting was used to quantify IL-8 mRNA expression in MNC and PMN.
- Enzyme-linked immunosorbent assay (ELISA) was employed to measure IL-8 protein levels in plasma.
- Chemotaxis assays were conducted to evaluate the biological activity of MNC, PMN, and plasma, specifically neutrophil chemoattractant activity.
Main Results:
- IL-8 mRNA expression in MNC and PMN, plasma IL-8 protein levels, and neutrophil chemoattractant activity were elevated during the acute phase of KD.
- These elevated levels, particularly IL-8 mRNA expression and plasma IL-8 protein, were significantly increased further following IVIG therapy.
- While overall neutrophil chemoattractant activity increased, the chemotactic response of neutrophils (but not monocytes) to F-met-leu-phe decreased post-IVIG treatment.
Conclusions:
- Increased IL-8 expression in PMN and MNC, along with elevated plasma IL-8 levels, occurs in KD patients receiving IVIG.
- The observed decrease in neutrophil chemotactic activity post-IVIG may suggest a mechanism to limit neutrophil accumulation at inflammatory sites.
- These findings suggest that IVIG therapy might mitigate the risk of coronary artery aneurysm formation in KD by modulating IL-8-mediated neutrophil recruitment.