title: CC10 reduces inflammation in meconium aspiration syndrome in newborn piglets.
abstract: Complications from meconium aspiration syndrome (MAS) remain significant despite a variety of therapeutic interventions. Clara cell protein (CC10) is a novel anti-inflammatory agent that can also inhibit phospholipase A2 (PLA2) (an important component of meconium). The present study examined whether administration of recombinant human CC10 (rhCC10) would reduce inflammation and improve lung function in a piglet model of MAS. Following meconium instillation, piglets exhibited significant physiologic dysfunction that improved significantly after surfactant administration. Analysis of tracheal aspirates revealed significant increases in both tumor necrosis factor (TNF) alpha and interleukin (IL)-8 after meconium instillation. rhCC10-treated animals had significantly lower TNF-alpha levels at 24 h (561 +/- 321 versus 1357 +/- 675 pg/mL, p < 0.05) compared with saline controls. There were no differences between rhCC10-treated and untreated groups with respect to other measured physiologic variables or inflammatory markers, including secretory PLA2 activity. Histologic analyses revealed marked inflammatory infiltrates and thickened alveolar walls, but no significant differences among rhCC10 and control animals. Newborn piglets with MAS have significant physiologic dysfunction, marked inflammatory changes and histologic abnormalities, which was partially counteracted by a single dose of exogenous surfactant and rhCC10.
authors.affiliation: Department of Pediatrics, The CardioPulmonary Research Institute, Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York 11501, USA. rangert@winthrop.org
authors.forename: Robert M
authors.initials: RM
authors.lastname: Angert
authors.forename: Aprile L
authors.initials: AL
authors.lastname: Pilon
authors.forename: Darrin
authors.initials: D
authors.lastname: Chester
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Davis
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008470:Meconium / Q000378:metabolism; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D014598:Uteroglobin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; D014409:Tumor Necrosis Factor-alpha; D014598:Uteroglobin; D054497:Phospholipases A2, Secretory