[Role of interleukin-5 in immune regulation and inflammation]

IL-5 is produced mainly by activated Th2 and mast cells. High level of IL-5 mRNA expression is detected in c-kit- cells in the lung, spleen, stomach and small intestine in RAG2-/- mice, suggesting the IL-5 production by non-T/non-mast/non-eosinophils. The IL-5R consists of two distinct membrane proteins, IL-5Ralpha and betac. The binding of IL-5 occurs through the IL-5Ralpha, and the betac forms a high-affinity IL-5R in combination with the IL-5Ralpha and transduces signals into nuclei. Activation of Btk and Jak2 kinases, rapid tyrosine phosphorylation of betac, adaptor proteins and transcription factors STAT5; and inductions of transcription of several nuclear proto-oncogenes are essential for the IL-5 signal transduction. Transgenic mice expressing the IL-5 gene exhibit elevated levels of serum IgM, IgA and IgE, increase in numbers of B-1 cells and eosinophils, and show persistent eosinophilia. Functional analysis of the IL-5Ralpha-/- and IL-5-/- mice revealed that IL-5 plays critical roles in the homeostatic proliferation, cell survival and activation of mature B-1 cells and regulates IgA production in the mucosal tissues in response to LPS. We also found that IL-5 can induce mu to gamma1 class-switch recombination in activated B-2 cells by activating AID and Blimp-1. Taking together, IL-5 plays important roles in terminal differentiation of B-lineage cells. In humans, IL-5 preferentially acts on eosinophil precursors and mature eosinophils to prolong maturation, survival and activation. Humanized anti-IL-5 mAb treatment for asthmatic patients was shown to reduce 100% for blood eosinophils but does not deplete airway or bone marrow eosinophils. No significant changes in airway hyper-responsiveness and peak flow recordings between the anti-IL-5 and placebo-treated groups were reported. At this moment, the role of IL-5 and eosinophil in allergic inflammation remains uncertain.