{"doi":"10.1002/ctm2.412","title":"Serum amlyoid A: An inflammatory adipokine mediating postburn outcomes","abstract":"Dear Editor, Burn trauma is associated with increased mortality rates despite many key advances and therapeutic strategies to improve patient care.1 One of the main drivers of poor outcomes in these patients is the complex yet overwhelming chronic inflammation that occurs in response to the injury.2 Unfortunately, the mechanisms, and in particular the signaling circuitry that facilitates persistent inflammation in these patients are essentially unknown. We report here that the acute phase protein serum amyloid A (SAA) mediates chronic inflammation and poor outcomes in both burn and septic burn patients. The inflammatory and prognostic potential of SAA has only been previously studied in context of heart disease and neonatal sepsis, leaving its potential pathogenic role in other conditions largely unexplored.3, 4 Therefore, in this present study we first characterized the kinetics of circulating SAA in both burn patients and septic burn patients relative to nonburn controls (Supplemental Table 1). Interestingly, circulating SAA levels persisted post the acute phase (>14 days) in both patient groups, with septic burn patients showing a greater increase in magnitude at both time (acute and late) points relative to burn patients (Figure 1A and B). Furthermore, when we profiled SAA levels in burn patients who succumbed to the injury, SAA levels were significantly higher in the nonsurvivors relative to burn patients who survived the injury (Figure 1C). Increased plasma SAA levels also paralleled an increase in the pro-inflammatory cytokine interleukin 1 beta (IL-1β), with septic burn patients showing a greater increase at both time (acute and late) points relative to nonseptic burn patients (Figure 1D). We further explored the inflammatory inducing effects of SAA using differentiated human THP-1 monocytes (Figure 1E). Differentiated human THP-1 macrophages stimulated with recombinant human SAA showed dramatic increases in the gene and protein expression of pro-inflammatory cytokines IL-6 and IL-1β (Figure 1F–I). Interestingly, SAA stimulation in macrophages evoked a similar pro-inflammatory cytokine profile to that of lipopolysaccharide (LPS), a well-established pro-inflammatory endotoxin. In corroboration of our clinical findings, mice subjected to either a 30% total body surface area burn injury and or a two-hit burn + Pseudomonas aeruginosa (PA) infection to mimic postburn sepsis, and also showed a greater increase in plasma SAA levels and IL-1β, with burn septic mice showing a greater increase in magnitude relative to the burn group (Figure S1A–C). To more directly link chronic SAA levels with poor outcomes, we injected septic burn mice with recombinant SAA daily for 1 week. Daily administration of SAA in septic burn mice significantly induced lethality and increased mortality (100 vs. 20%) relative to untreated septic burn mice (Figure S1D). Additionally, bone marrow–derived macrophages (BMDMs) isolated from postburn mice stimulated with SAA also showed dramatic increases in the gene and protein expression of the pro-inflammatory cytokines IL-6 and IL-1β (Figure S2A–E). Although the liver has previously been reported to be the main production site for SAA, recent findings in obese patients have implicated the adipose tissue as another key producer of SAA.5-8 Given the metabolic etiology of obese patients (insulin resistance, hyperglycemia, inflammation) also experienced by burn patients following the injury, we hypothesized that the chronic circulating SAA levels observed in burn patients may arise from the adipose tissue. To test this hypothesis, we measured SAA expression in subcutaneous white adipose tissue (sWAT) collected from burn patients and nonburn controls (Table S1). sWAT from burn patients showed significant gene and protein expression of SAA compared to nonburn controls (Figure 2A and B). These findings were further corroborated by our ex vivo fat culture findings, in which secretomes from cultured sWAT isolated fr","journal":"Clinical and Translational Medicine","year":2021,"id":203540,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"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":759508,"name":"Mile Stanojcic","orcid":"0000-0002-9022-2365","position":1,"is_corresponding":false},{"id":385635,"name":"Nancy Yu","orcid":"0000-0001-8321-8141","position":2,"is_corresponding":false},{"id":784776,"name":"Osai Samadi","orcid":"0000-0002-7445-158X","position":3,"is_corresponding":false},{"id":784777,"name":"Ali-Reza Sadri","orcid":"0000-0002-2963-5531","position":4,"is_corresponding":false},{"id":287973,"name":"Roohi Vinaik","orcid":"0000-0001-9936-3044","position":5,"is_corresponding":false},{"id":784778,"name":"Natalie G. Coburn","orcid":"0000-0002-5313-717X","position":6,"is_corresponding":false},{"id":287976,"name":"Marc G. Jeschke","orcid":"0000-0003-0870-1664","position":7,"is_corresponding":false},{"id":142784,"name":"Abdikarim Abdullahi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-18T23:51:18.050175Z","pmid":"34185405","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":[]}