title: The immunological landscape in necrotising enterocolitis.
abstract: Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.
authors.affiliation: Ritchie Centre,Hudson Institute of Medical Research,Melbourne,Australia.
authors.forename: Steven X
authors.initials: SX
authors.lastname: Cho
authors.affiliation: Ritchie Centre,Hudson Institute of Medical Research,Melbourne,Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Berger
authors.affiliation: Ritchie Centre,Hudson Institute of Medical Research,Melbourne,Australia.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Nold-Petry
authors.affiliation: Ritchie Centre,Hudson Institute of Medical Research,Melbourne,Australia.
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Nold
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility / Q000276:immunology* / Q000378:metabolism; D020345:Enterocolitis, Necrotizing / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007109:Immunity; D007155:Immunologic Factors / Q000378:metabolism; D063868:Patient Outcome Assessment; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition