Interleukin-13 Production by Peripheral Blood Mononuclear Cells from Pediatric Asthma Patients and its Modulation by Regulatory Cytokines

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Interleukin (IL)-13, a T-helper type 2 (Th2) cytokine, is thought to be involved in the airway hyperreactivity (AHR) of asthma patients. To investigate the role of IL-13 in pediatric patients with Dermatophagoides farinae (Df)-sensitive atopic and Df-insensitive non-atopic asthma, we evaluated the serum level of IL-13 and IL-13 production by primary cultured peripheral blood mononuclear cells (PBMCs) after stimulation with Df antigen and regulatory cytokines. Serum levels of IL-13 were significantly higher in active asthmatic children than in normal subjects. The levels were also significantly higher during excerbation of asthma than those during the attack-free state. Spontaneous production of IL-13 by PBMCs from Df-sensitive asthma patients was higher than by cells from control subjects, while IL-13 production by cells from Df-insensitive asthma patients was comparable to that by control cells. Upon stimulation with 1 μg/ml of Df, production of IL-13 by cells from Df-sensitive patients, but not cells from Df-insensitive patients or controls, was increased when compared to that without stimulation. Production of IL-13 by phytohemagglutinin (PHA)-stimulated cells was markedly increased in both types of asthma, although the increase was greater in Df-sensitive asthma patients than in Df-insensitive asthma patients. In contrast, PHA-stimulated cells from control subjects only produced a small amount of IL-13. In Df-insensitive, non-atopic patients, AHR seemed likely to be related to IL-13 because IL-13 production by PHA-stimulated cells from asthma patients in remission (most of whom still had normal lung function parameters such as forced expiratory volume (FEV_1), was unchanged compared with that by cells from patients with active asthma, despite of the decrease of IL-13 induced by stimulation with the relevant antigen. These results indicate that IL-13 is not only associated with allergic inflammation but also with the AHR in patients who have antigen-insensitive asthma. Finally, IL-13 synthesis by both PHA- and Df-stimulated PBMCs from Df-sensitive patients was down-regulated by addition of IL-12, transforming growth factor (TGF)-β_1, and IL-10. These regulatory cytokines are likely to be involved in the modulation of IL-13 activity, and in outgrowing asthma.
北里大学の論文
2002-08-31

Interleukin-13 Production by Peripheral Blood Mononuclear Cells from Pediatric Asthma Patients and its Modulation by Regulatory Cytokines

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