Roles of PI3K pan-inhibitors and PI3K-δ inhibitors in allergic lung inflammation: a systematic review and meta-analysis

Meta-analysis can be applied to study the effectiveness of the summary estimates for experimental papers, producing objective and unbiased results. We investigated the effects of phosphoinositide-3-kinase (PI3K) on the inflammatory profile in allergic mouse models, which are currently under development in signal transduction materials. PubMed, EMBASE and Web of Science databases were searched for relevant literature using the search terms " PI3K inhibitor" and "allergy" or "asthma". Cochrane Review Manager and R were used for handling continuous variables. The primary outcomes of the inflammatory profile were divided into cell counts and inflammatory cytokines. We used a random effects model to draw a forest plot. Through the database search and subsequent selection, 17 articles were identified. Regarding the cell counts, both the PI3K pan-inhibitors and PI3K-delta inhibitors effectively reduced the total cell counts, eosinophils, neutrophils and lymphocytes. In contrast to PI3K-delta inhibitors, PI3K pan-inhibitors effectively reduced macrophages. Regarding the inflammatory cytokines, PI3K pan-inhibitors and PI3K-delta inhibitors effectively reduced total IgE, IL-4, IL-5, IL-13, TNF-alpha, IL-1 beta, VEGF and had no effect on IL-6. Compared to the PI3K pan-inhibitors, which block all pathways, selective PI3K-delta inhibitors are expected to be relatively less toxic. Regarding the efficacy, PI3K-delta inhibitors have at least the same or better efficacy than PI3K pan-inhibitors in effector cells and inflammatory mediators.