Idelalisib induces apoptosis in the lymphoid tissues and impairs lung function in mice.
Idelalisib, an inhibitor of the phosphatidylinositol-3-kinase p110δ subunit (PI3Kδ), is approved for treating lymphoid malignancy. The drug is associated with hematopoietic and pulmonary toxicities, which limit its clinical use. However, the toxicity mechanisms are not completely elucidated. In this study, mice were intraperitoneally injected with idelalisib (40 or 80 µg/g) or dimethyl sulfoxide for five days every week for up to four weeks to evaluate the changes in the thymus, spleen, and pulmonary functions. Idelalisib treatment induced thymic involution, decreased CD4+/CD8+ T-cell population, and increased CD4-/CD8- T-cell population. In the spleen, idelalisib dose dependently decreased the lymphocyte viability and cell count. Idelalisib-treated mice exhibited enhanced cleaved caspase-3 expression in the thymus, spleen, and lung tissues. Idelalisib augmented thoracic and airway resistance and decreased thoracic compliance. Thus, PI3Kδ has physiological roles in T-cell development and airway function. Monitoring drug toxicity is important for developing follow-up compounds that target PI3Kδ signalling.
['George|Junu A|JA|', 'Alshebli|Zainab|Z|', 'Alneyadi|Asma|A|', 'Al Mukhaini|Noura|N|', 'Al-Salam|Suhail|S|', 'Sudhadevi|Manjusha|M|', 'Souid|Abdul-Kader|AK|', 'Alsuwaidi|Ahmed R|AR|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D004305:Dose-Response Relationship, Drug D006801:Humans D007274:Injections, Intraperitoneal D008168:Lung D008221:Lymphoid Tissue D051379:Mice D008807:Mice, Inbred BALB C D000081082:Phosphoinositide-3 Kinase Inhibitors D011687:Purines D052999:Quinazolinones D015398:Signal Transduction D013154:Spleen D013950:Thymus Gland
idelalisib thymus spleen caspase-3 airway resistance PI3K delta