American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2014
Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.
Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects. ⋯ Administration of corticosteroids in pediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.
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Am. J. Respir. Crit. Care Med. · Apr 2014
Comparative StudyZ alpha-1 antitrypsin confers a pro-inflammatory phenotype that contributes to COPD.
Severe α1-antitrypsin deficiency caused by the Z variant (Glu342Lys; ZZ-AT) is a well-known genetic cause for emphysema. Although severe lack of antiproteinase protection is the critical etiologic factor for ZZ-AT-associated chronic obstructive pulmonary disease (COPD), some reports have suggested enhanced lung inflammation as a factor in ZZ-AT homozygotes. ⋯ We show here that aggregation of intracellular mutant Z-AT invokes a specific deleterious cellular inflammatory phenotype in COPD. Oxidant-induced intracellular polymerization of Z-AT in epithelial cells causes ER stress, and promotes excess cytokine and cellular inflammation. This pathway is likely to contribute to the development of COPD in ZZ-AT homozygotes, and therefore merits further investigation.