{"doi":"10.1016/j.ebiom.2020.103002","title":"Modulation of macrophage polarity for treatment of acute pancreatitis: Are we there yet?","abstract":"Acute pancreatitis (AP) is a common cause of hospitalizations, morbidity and mortality in the USA [[1]Peery AF Crockett SD Murphy CC et al.Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018.Gastroenterology. 2019; 156 (254-72.e11)Summary Full Text Full Text PDF PubMed Scopus (697) Google Scholar]. Today, it is clear that the novel therapeutics against this formidable disease will have to target inflammation. Given the central role of Monocytes/macrophages in orchestrating the inflammation during AP, they have emerged as an obvious cellular target [[2]Xue J Sharma V Habtezion A Immune cells and immune-based therapy in pancreatitis.Immunol Res. 2014; 58: 378-386Crossref PubMed Scopus (51) Google Scholar]. However, it has also become clear that we need to modulate, and not completely abrogate this important player. Depending on its phenotypic characteristics, various subtypes or states of polarization of this important regulator of inflammation may in fact be critical for quietening inflammation and beginning repair. To take things in perspective, the polarization of macrophages should be considered as a spectrum, of which the classical (M1) and alternative (M2) activation states represent the two extremes [[3]Das A Sinha M Datta S et al.Monocyte and macrophage plasticity in tissue repair and regeneration.Am J Pathol. 2015; 185: 2596-2606Summary Full Text Full Text PDF PubMed Scopus (420) Google Scholar]. Studies till date suggest that while M1 macrophages are believed to initiate as well as promote inflammation during acute phase, M2 phenotype dominates and potentially promotes repair during recovery. For instance, it has been demonstrated that Ly-6Chi monocyte subset (which may correspond to M1 macrophages) increases the severity of AP by producing TNF-α, and their depletion (using diphtheria toxin inducible Ly-6Chi monocyte depletion) prior to induction of AP in CD11b-DTR mice, reduces AP severity [[4]Perides G Weiss ER Michael ES Laukkarinen JM Duffield JS Steer ML TNF-alpha-dependent regulation of acute pancreatitis severity by Ly-6C(hi) monocytes in mice.J Biol Chem. 2011; 286: 13327-13335Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar]. The Yin-Yang of macrophage is further underscored by the fact that while prophylactic depletion of macrophages using clodronate 24 h before initiation of injury has a protective effect [[5]Saeki K Kanai T Nakano M et al.CCL2-induced migration and SOCS3-mediated activation of macrophages are involved in cerulein-induced pancreatitis in mice.Gastroenterology. 2012; 142 (e9): 1010-1020Summary Full Text Full Text PDF PubMed Scopus (66) Google Scholar], depletion of macrophage later in the process led to decrease in PDX-1 positive cells and failure of regeneration [[6]Criscimanna A Coudriet GM Gittes GK Piganelli JD Esni F Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and beta-cell regeneration in mice.Gastroenterology. 2014; 147 (e11): 1106-1118Summary Full Text Full Text PDF PubMed Scopus (77) Google Scholar]. To complicate the matter even more, it has recently been shown that Systemic Immune Response Syndrome (SIRS) and Compensatory anti-inflammatory response (CARS) in AP are initiated early on and progress simultaneously, but not sequentially as was the previous consensus [[7]Sendler M van den Brandt C Glaubitz J et al.NLRP3 inflammasome regulates development of systemic inflammatory response and compensatory anti-inflammatory response syndromes in mice with acute pancreatitis.Gastroenterology. 2020; 158 (e14): 253-269Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar,[8]Iyer S Bawa EP Tarique M Dudeja V Know thy enemy-understanding the role of inflammation in severe acute pancreatitis.Gastroenterology. 2020; 158: 46-48Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar]. It appears that while the cellular target for novel therapeutic strategies i.e., mac","journal":"EBioMedicine","year":2020,"id":74815,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":390974,"name":"Ejas Palathingal Bava","orcid":"0000-0003-1719-2451","position":1,"is_corresponding":false},{"id":390975,"name":"Srikanth Iyer","orcid":"0000-0002-2030-4867","position":2,"is_corresponding":false},{"id":390976,"name":"Vikas Dudeja","orcid":"0000-0001-9224-777X","position":3,"is_corresponding":false},{"id":390973,"name":"Preeti Sahay","orcid":"0000-0002-2822-8627","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-18T21:46:11.663457Z","pmid":"32979834","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":[]}