Adult serum cytokine concentrations and the persistence of asthma.

BACKGROUND: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. METHODS: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. RESULTS: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. CONCLUSION: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.

Morphometric analysis of renal proximal tubules in cadmium-treated rats.

The morphological changes in renal proximal tubules of Sprague Dawley rats given acute or chronic exposure to cadmium were analysed. Cadmium chloride was administered either by five subcutaneous injections of cadmium at 2 mg kg-1 body weight or in drinking water at 100 micrograms ml-1 for 39 weeks. The mean cadmium concentration in the kidneys of these rats was 45 and 102 micrograms g-1 wet weight respectively. The rats were anaesthetized and the kidneys were fixed by perfusion and processed for electron microscopy. Proximal tubule profiles were larger in the acute exposure rats. The brush border in both groups of treated rats was shorter and there were focal areas of loss of microvilli. The surface density of microvillus membrane per unit cell volume was reduced by 25% and 19% for chronic and acute dosed rats respectively. There were few significant changes in organelles detected by morphometric analysis of the entire kidney tissue, however there was a reduction in volume density of lysosomes following chronic exposure and individual necrotic cells and distorted nuclei were observed. The morphological changes observed in chronic and acute dosed rats were consistent with a primary site of toxic insult on the apical plasma membrane. There appeared to be no evidence for change in fluid and electrolyte homeostasis in the epithelium. The results suggest that the cadmium may produce a selective deficit of transport mechanisms for macromolecules.