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delivery in tissues. Indeed, the exercise performance variables that displayed an association with the immune variables, including elastase activity, were mainly related to respiration (oxygen uptake and RER). On the other hand, intracellular elastase activity in peripheral monocytes/lym-phocytes was assessed. Peripheral blood characteristics may not correspond to the alterations in the capillaries surrounding lung alveoli. In addition, it seems unlikely that intracellular elastase in peripheral blood is capable of causing lung tissue damage, as seen in other diseases like cystic fibrosis (7). In an animal model of cystic fibrosis, elastase degraded several alveolar surfactant proteins important for alveolar tension reduction and innate immune function (1). Apart from one study showing an association between immune activation and bronchial hyperresponsiveness (17), we are unaware of experimental data providing evidence for impairments in lung tissue in CFS patients. An increased number of cytotoxic T-cells, accompanied by a decreased amount of naive T-cells, was observed in CFS patients with bronchial hyperresponsiveness compared with CFS patients without bronchial hyperresponsiveness (17). T-cells release elastase to establish their cytotoxicity, linking the current with our previous observations.
RNase L activity and proteolysis correlated strongly with both the resting RER and the oxygen uptake at RER = 1. 0.
These observations may be related to the increased elas-tase activity: elastase has been identified as one of the proteolytic enzymes responsible for RNase L cleavage (5). Whether RNase L proteolysis triggers a channelopa-thy and consequent intracellular hypomagnesaemia in skeletal muscles and transient hypoglycemia, as suggested in the introduction, requires further investigation. Furthermore, it was hypothesized that PKR activation and consequent elevated NO levels might limit exercise performance in CFS patients. The current observations do not support this hypothesis; although PKR activation appeared to be a determinant of exercise performance, no associations between NO levels and exercise performance were observed. However, further studying of the hypothesis assessing extracellular NO levels during the exercise challenge rather than resting NO levels in peripheral monocytes/lymphocytes is warranted.
Addressing the study limitations, the cross-sectional nature of the study should be acknowledged. To establish a causal relationship, further study of these interactions in a larger study sample, using a prospective longitudinal design, is required. In addition, given that a number of correlations were significant at the 0. 05, but not at the 0. 01 level, one can argue that the sample size lacked strength. Depending on the parameter of interest, the power of the study varied between 63 and 81%, with an associated probability of Type II error of 37 and 19% respectively. Because a power of 80% was considered fair, increasing the sample size would only be appropriate to reveal statistically significant correlations between RNase L activity and the percentage of age-predicted target heart rate achieved, and between the RNase L-ratio and the workload at RER = 1. 0. Increasing the sample
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