CC10 Reduces Inflammation in Meconium Aspiration Syndrome in Newborn Piglets

• Published in: Pediatric research Vol. 62; no. 6; pp. 684 - 688
• Main Authors: ANGERT, Robert M, PILON, Aprile L, CHESTER, Darrin, DAVIS, Jonathan M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.12.2007
• Subjects: Animals; Animals, Newborn; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Disease Models, Animal; Drug Therapy, Combination; Enzyme Inhibitors - pharmacology; General aspects; Humans; Infant, Newborn; Interleukin-8 - blood; Interleukin-8 - metabolism; Lung - drug effects; Lung - enzymology; Lung - metabolism; Lung - pathology; Lung - physiopathology; Meconium - metabolism; Meconium Aspiration Syndrome - drug therapy; Meconium Aspiration Syndrome - metabolism; Meconium Aspiration Syndrome - pathology; Meconium Aspiration Syndrome - physiopathology; Medical sciences; Phospholipases A2, Secretory - antagonists & inhibitors; Phospholipases A2, Secretory - metabolism; Pulmonary Surfactants - pharmacology; Recombinant Proteins - pharmacology; Swine; Time Factors; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - metabolism; Uteroglobin - administration & dosage; Uteroglobin - pharmacology; Uteroglobin - therapeutic use; Lung disease; Pediatrics; Respiratory disease; Inflammation; Trauma; Pig; Vertebrata; Mammalia; Aspiration pneumonia; Newborn animal; Meconium; Foreign body; Artiodactyla; Ungulata
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/PDR.0b013e31815a5632

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.