Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in bleomycin (BLM)-induced lung injury and subsequent fibrotic changes remains to be determined. We evaluated the role of IL-6 in the lung inflammatory changes induced by BLM using wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. The mice were treated intratracheally with 1 mg/kg BLM and killed 2, 7, or 21 days later. Lung Inflammation in the acute phase (Days 2 and 7) was assessed by differential cell counts in bronchoalveolar lavage (BAL) fluid and cytokine levels in the lung. Lung fibrotic changes were evaluated on Day 21 by histopathology and collagen assay. On Day 2, BLM administration induced significant increases in the numbers of total cells, macrophages, and neutrophils in BAL fluid, which were attenuated in IL-6(-/-) mice (P < 0.05). Lung pathology also showed inflammatory cell accumulation, which was attenuated in the IL-6(-/-) mice compared with WT mice. In WT mice, elevated levels of TGF-beta(1) and CCL3 were observed 2 and 7 days after BLM challenge, respectively. On Day 7, BLM-induced inflammatory cell accumulation did not differ between the genotypes. Lung pathology 21 days after BLM challenge revealed significant fibrotic changes with increased collagen content, which was attenuated in IL-6(-/-) mice. Although the TGF-beta(1) level in the lung did not differ between the genotypes on Day 21, CCL3 was significantly lower in IL-6(-/-) mice. These results indicate that IL-6 may play an important role in the pathogenesis of BLM-induced lung injury and subsequent fibrotic changes.

RAGE plays an important role in the pathogenesis of LPS-induced lung injury in mice. It was suggested that sRAGE should be tested as a treatment modality in other models of acute lung injury.

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Enlarged tonsils, adenoids, and chronic respiratory problems have been associated with the compensatory adaptations of natural head posture (NHP) in children. Recently, it has been shown that adult patients with Obstructive Sleep Apnoea (OSA) also tend to exhibit a craniocervical extension (CCE) with a forward head posture (FHP). This study was designed to search for some characteristics of OSA patients that may be related to these adaptive changes in NHP. Overnight polysomnographic, demographic, and cephalometric records of 252 adult male subjects with various types of skeletal patterns and dental conditions were examined. Apnoea Index (AI) and Apnoea + Hypopnoea Index (AHI) variables were assessed to separate the non-apnoeic snorers (n = 35), and mild (n = 101), moderate (n = 63), and severe (n = 53) OSA groups. Results of the Tukey tests revealed that severe OSA patients had a greater tendency to exhibit a CCE with a FHP (P < or = 0.05 to P < or = 0.001). Differences in head extension (NSL.VER) between groups could not be identified. Pearson's 'r' correlation coefficients revealed that the CCE and FHP in OSA patients were associated with a higher disease severity, a longer and larger tongue, a lower hyoid bone position in relation to the mandibular plane, a smaller nasopharyngeal and a larger hypopharyngeal cross-sectional area, and a higher body mass index (P < or = 0.05 to P < or = 0.001). It is concluded that a CCE with a FHP is more likely to be seen in severe and obese OSA patients with certain morphological characteristics of the upper airway and related structures.

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