Rodríguez-Álvarez Y, Gerónimo-Pérez H, Garay-Pérez H, Castro-Velazco J, García-Illera G, Santos-Savio A

Language: English
References: 28
Page: 291-296
PDF size: 297.31 Kb.

ABSTRACT

Dysregulated expression of Interleukin (IL)-15 has been associated to several autoimmune and inflammatory diseases. In this sense, some agents that inhibit IL-15 activity have been developed as possible drugs to treat these pathologies. We have been working in two strategies to inhibit IL-15 activity, a peptide (named P8) that binds to the alpha subunit of the IL-15 receptor (IL-15R) and a vaccine based on active immunization with human IL-15 (hIL-15). To measure the biological activity of the IL-15 antagonists we used the proliferation assay in CTLL-2, a cell line that depends on IL-2/IL-15 to proliferate. In the current work we defined the conditions of the assay to determine the half maximal inhibitory concentration (IC₅₀) of the P8 peptide and the neutralizing titers of the sera from monkeys immunized with the anti-IL-15 vaccine. The specificity of the assay for IL-15 was documented using anti-IL-15 and anti-IL-2 specific antibodies. We also examined the specificity of the antagonists of IL-15 in presence of IL-2; neither the peptide nor the sera inhibited the cell proliferation induced by human IL-2. Finally, we evaluated the effect of commercial antibodies anti-hIL-15 and sera from mice immunized with hIL-15 on murine IL-15 (mIL-15). In this case, neither the antibodies nor the sera inhibited mIL-15; therefore, murine models are not useful to evaluate the effectiveness of anti-hIL-15 vaccine. The application of this assay allowed us to evaluate different strategies to inhibit the activity of IL-15 for its future development as drugs.

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