TY - JOUR T1 - Cytokine expression in the diaphragm of rats breathing against subacute hypoxic conditions JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4732 AU - M. Dominguez AU - S. Pascual AU - M. Sabaté AU - F. Sánchez AU - C. Casadevall AU - E. Barreiro AU - J. Gea Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4732.abstract N2 - COPD patients show muscle damage and an increase in the expression of local cytokines in their diaphragms. The paracrine role of these cytokines still remains controversial.Objective: To analyze the effects of subacute hypoxia on the diaphragm muscle.Methods: Wistar rats (n=8/group) were exposed to: (1) hypoxia (FIO2 0.10) +placebo, (2) normoxia +placebo, (3) hypoxia +Infliximab [monoclonal antibody that results in the blockade of TNF-α receptors], and (4) normoxia +Infliximab for 2 weeks in all cases. At the end of the study period diaphragm and gastrocnemius muscles as well as blood samples were obtained. Molecular and cellular indices of muscle damage, oxidative stress, cytokine expression and activation of regeneration pathways were obtained using morphometry, Western-blot, spectrophotometry, ELISA, luminometry and RT-PCR.Results: Although rats exposed to hypoxia showed higher levels of expression of different cytokines (TNF-α, IL-6, INF-g) in their diaphragms than the control animals (normoxia), no differences were observed in muscle damage, oxidative stress and biomarkers of muscle regeneration. Inhibition of TNF-α action in hypoxic animals resulted in an even higher expression of local cytokines with no relevant changes in the other variables when compared with hypoxic animals receiving placebo. No changes were observed in either limb muscle or blood in any of the groups.Conclusions: Hypoxia induces local inflammation in respiratory muscles of hypoxic rats. This effect appears to be selective for respiratory muscles and can be related to changes in their mechanical loading and its mismatching with the oxygen delivery to the muscle.Funded: SAF07-62719, CIBERES, SEPAR & SOCAP. ER -