Osteopontin (Opn) is important for T helper type 1 (T H 1) immunity and autoimmunity. However, the role of this cytokine in T H 2-mediated allergic disease as well as its effects on primary versus secondary antigenic encounters remain unclear. Here we demonstrate that OPN is expressed in the lungs of asthmatic individuals and that Opn-s, the secreted form of Opn, exerts opposing effects on mouse T H 2 effector responses and subsequent allergic airway disease: pro-inflammatory at primary systemic sensitization, and anti-inflammatory during secondary pulmonary antigenic challenge. These effects of Opn-s are mainly mediated by the regulation of T H 2-suppressing plasmacytoid dendritic cells (DCs) during primary sensitization and T H 2-promoting conventional DCs during secondary antigenic challenge. Therapeutic administration of recombinant Opn during pulmonary secondary antigenic challenge decreased established T H 2 responses and protected mice from allergic disease. These effects on T H 2 allergic responses suggest that Opn-s is an important therapeutic target and provide new insight into its role in immunity.

It is known that non-cachectic patients with chronic obstructive pulmonary disease (COPD) respond well to pulmonary rehabilitation, but whether cachectic COPD patients are capable of adaptive responses is both important and unknown.10 cachectic and 19 non-cachectic COPD patients undertook high-intensity cycling training, at the same relative intensity, for 45 min?day -1 , 3 days?week -1 for 10 weeks. Before and after rehabilitation vastus lateralis muscle biopsies were analysed morphologically and for the expression of muscle remodelling factors (insulin-like growth factor (IGF)-I, myogenic differentiation factor D (MyoD), tumour necrosis factor (TNF)-a, nuclear factor (NF)-kB and myostatin) and key components of ubiquitin-mediated proteolytic systems (muscle ring finger protein (MURF)-1 and Atrogin-1).Rehabilitation improved peak work-rate and the 6-min walk distance similarly in non-cachectic (18¡3% and 42¡13 m, respectively) and cachectic (16¡2% and 53¡16 m, respectively) patients, but quality of life only improved in non-cachectic COPD. Mean muscle fibre cross-sectional area increased in both groups, but significantly less in cachectic (7¡2%) than in non-cachectic (11¡2%) patients. Both groups equally decreased the proportion of type IIb fibres and increased muscle capillary/fibre ratio. IGF-I mRNA expression increased in both groups, but IGF-I protein levels increased more in non-cachectic COPD. MyoD was upregulated, whereas myostatin was downregulated at the mRNA and protein level only in non-cachectic patients. Whilst rehabilitation had no effect on TNF-a expression, it decreased the activation of the transcription factor NF-kB in both groups by the same amount. Atrogin-1 and MURF-1 expression were increased in cachectic COPD, but it was decreased in non-cachectic patients.Cachectic COPD patients partially retain the capacity for peripheral muscle remodelling in response to rehabilitation and are able to increase exercise capacity as much as those without cachexia, even if they exhibit both quantitative and qualitative differences in the type of muscle fibre remodelling in response to exercise training.

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Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation. This study investigated whether rehabilitative exercise training decreases the levels of systemic or local muscle inflammation or reverses the abnormalities associated with muscle deconditioning. Methods: Fifteen patients with COPD (mean (SE) forced expiratory volume in 1 s 36 (4)% predicted) undertook high-intensity exercise training 3 days/week for 10 weeks. Before and after the training programme the concentration of tumour necrosis factor a (TNFa), interleukin-6 (IL-6) and C-reactive protein (CRP) in plasma was determined by ELISA, and vastus lateralis mRNA expression of TNFa, IL-6, total insulinlike growth factor-I (IGF-I) and its isoform mechanogrowth factor (MGF) and myogenic differentiation factor D (MyoD) were assessed by real-time PCR. Protein levels of TNFa, IGF-I and MyoD were measured by Western blotting. Results: Rehabilitation improved peak exercise work rate by 10 (2%) (p = 0.004) and mean fibre crosssectional area from 4061 (254) mm 2 to 4581 (241) mm 2 (p = 0.001). Plasma inflammatory mediators and vastus lateralis expression of TNFa and IL-6 were not significantly modified by training. In contrast, there was a significant increase in mRNA expression of IGF-I (by 67 (22)%; p = 0.044), MGF (by 67 (15)%; p = 0.002) and MyoD (by 116 (30)%; p = 0.001). The increase observed at the mRNA level was also seen at the protein level for IGF-I (by 72 (36)%; p = 0.046) and MyoD (by 67 (21)%; p = 0.012). Conclusions: Pulmonary rehabilitation can induce peripheral muscle adaptations and modifications in factors regulating skeletal muscle hypertrophy and regeneration without decreasing the levels of systemic or local muscle inflammation.