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Strenuous resistive breathing induces plasma cytokines that do not originate from circulating monocytes. We hypothesized that cytokine production is induced inside the diaphragm in response to resistive loading. Anesthetized, tracheostomized, spontaneously breathing Sprague-Dawley rats were subjected to 1, 3, or 6 hours of inspiratory resistive loading, corresponding to 45-50% of the maximum inspiratory pressure. Unloaded sham-operated rats breathing spontaneously served as control animals. The diaphragm and the gastrocnemius muscles were excised at the end of the loading period, and messenger ribonucleic acid expression of tumor necrosis factor-alpha, tumor necrosis factor-beta, interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, and two housekeeping genes was analyzed using multiprobe RNase protection assay. IL-6, IL-1beta, and, to lesser extents, tumor necrosis factor-alpha, IL-10, IFN-gamma, and IL-4 were significantly increased in a time-dependent fashion in the diaphragms but not the gastrocnemius of loaded animals or in the diaphragm of control animals. Elevation of protein levels of IL-6 and IL-1beta in the diaphragm of loaded animals was confirmed with immunoblotting. Immunostaining revealed IL-6 protein localization inside diaphragmatic muscle fibers. We conclude that increased ventilatory muscle activity during resistive loading induces differential elevation of proinflammatory and antiinflammatory cytokine gene expression in the ventilatory muscles.

AIM:The significance of preoperative serum IL-6, TNF and CRP levels in the progression of colorectal cancer (CRC) has not been fully elucidated. Our intention was to investigate their role and identify their prognostic significance. METHODS:The IL-6, TNF and CRP levels were measured in 74 CRC patients and the relationships between their elevations and both the clinicopathological factors and prognosis of patients w ere inves tigated. Serum concentrations of human IL-6 and TNF were determined by enzyme-linked immunosorbent assay (ELISA). CRP was measured by an immunoturbinometric method. RESULTS:Median IL-6, TNF and CRP levels were significantly higher in CRC patients than in normal controls. High levels of serum IL-6, TNF and CRP were correlated with larger tumor size. Furthermore, high IL-6 and high CRP levels were associated with reduced overall survival.CONCLUSION: Serum IL-6, TNF and CRP levels definitely increase in CRC patients. Pre-operative serum elevation of IL-6 and CRP was thus found to be predictor of the prognosis of CRC patients. The clinical value of TNF in CRC needs to be further investigated.

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study, we evaluated the differential influence of chronic treadmill training (30 m/min, 15% incline, 1 h/day, 5 days/wk) on nitric oxide (NO) production and NO synthase (NOS) isoform expression as well as 3-nitrotyrosine formation (footprint of peroxynitrite) both in limb (gastrocnemius) and ventilatory (diaphragm) muscles. A group of exercise-trained rats and a control group (no training) were examined after a 4-wk experimental period. Exercise training elicited an approximate fourfold rise in gastrocnemius NOS activity and augmented protein expression of the endothelial (eNOS) and neuronal (nNOS) isoforms of NOS to ϳ480% and 240%, respectively. Qualitatively similar but quantitatively smaller elevations in NOS activity and eNOS and nNOS expression were observed in the diaphragm. No detectable inducible NOS (iNOS) protein expression was found in any of the muscle samples.