{"doi":"10.3390/cells10092173","title":"Early-Released Interleukin-10 Significantly Inhibits Lipopolysaccharide-Elicited Neuroinflammation In Vitro","abstract":"Anti-inflammatory cytokine interleukin (IL)-10 is pivotal for limiting excessive inflammation in the central nervous system. Reports show that lipopolysaccharide (LPS)-induced microglial IL-10 emerges in a delayed manner in vitro and in vivo, lagging behind proinflammatory cytokines to facilitate the resolution of neuroinflammation. We hypothesized that IL-10 releases quite quickly based on our pilot investigation. Here, we uncovered a bimodal expression of microglial IL-10 gene transcription induced by LPS in mouse primary mixed glial cultures. This pattern consisted of a short brief early-phase and a long-lived late-phase, enabling the production of IL-10 protein in a rapid manner. The removal and addition of IL-10 protein assays indicated that early-released IL-10 exerted potent modulatory effects on neuroinflammation at picomolar levels, and IL-10 released at the onset of neuroinflammation is tightly controlled. We further showed that the early-released, but not the late-released, IL-10 was crucial for mediating and potentiating the anti-inflammatory function of a β2-adrenergic receptor agonist salmeterol. This study in vitro highlights the essential role of early-released IL-10 in regulating the appropriate degree of neuroinflammation, overturning the previous notion that microglial IL-10 produces and functions in a delayed manner and providing new insights into anti-inflammatory mechanisms-mediated neuroimmune homeostasis.","journal":"Cells","year":2021,"id":175680,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":716933,"name":"Pei Yu","orcid":"0000-0001-6729-4443","position":1,"is_corresponding":false},{"id":716934,"name":"Yi Li","orcid":"0000-0001-7165-7251","position":2,"is_corresponding":false},{"id":276861,"name":"Zhan Zhao","orcid":"0000-0002-0385-5595","position":3,"is_corresponding":false},{"id":717510,"name":"Xiaomei Wu","orcid":null,"position":4,"is_corresponding":false},{"id":716935,"name":"Lu Zhang","orcid":"0000-0001-5695-1540","position":5,"is_corresponding":false},{"id":716936,"name":"Jing Feng","orcid":"0000-0003-0604-3581","position":6,"is_corresponding":false},{"id":276867,"name":"Jau‐Shyong Hong","orcid":"0000-0002-3056-8401","position":7,"is_corresponding":false},{"id":276862,"name":"Yubao Wang","orcid":"0000-0003-0332-7984","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:47:15.431199Z","pmid":"34571824","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}