We have investigated the presence of regulated on activation, normal T-cell expressed and probably secreted (RANTES), macrophage inflammatory peptide-1 alpha (MIP-1 alpha), and macrophage chemotactic peptide (MCP-1) in the bronchoalveolar lavage fluid (BALF) obtained from normal (n = 7) and stable asthmatic subjects (n = 8), and studied their kinetic release into asthmatic airways following endobronchial allergen challenge (n = 18). Measurements of RANTES, MIP-1 alpha, and MCP-1 in 10 times (10x) concentrated BALF showed that these three chemokines were present in both normal controls and stable asthmatic patients, but no significant difference between the two groups was found in the levels of the three chemokines. However, at 4 h after allergen challenge, BALF levels of RANTES, MIP-1 alpha, and MCP-1 were significantly increased in fluid obtained from the allergen-challenge site when compared with the saline-challenge control site (median: 175 pg/ml versus 11.5 pg/ml, 258 pg/ml versus 88 pg/ml, and 900 pg/ml versus 450 pg/ml, respectively). At 24 h, levels of the three chemokines returned to baseline values. To investigate whether cells in BALF obtained 4 h after allergen exposure release chemokines, they were cultured for 24 h. BALF cells from the allergen site released more RANTES and MCP-1 than those from the saline site, but released similar amounts of MIP-1 alpha. These findings suggest that RANTES, MIP-1 alpha, and MCP-1 may regulate cell trafficking in asthma in response to allergen exposure.

Our results suggest that structural injury develops early in the natural history of the renal allograft and is mediated, in part, by the early up-regulation of profibrotic growth factors. We have determined that calcineurin inhibitors, in particular cyclosporine, and acute rejection episodes are key factors in the development of renal structural injury.

The thyrotrophin receptor (TSHR) provides an autoantigenic link between the thyroid and orbit in Graves' (GD) and thyroid eye diseases (TED). We measured TSHR transcripts in different fat depots to determine whether TSHR expression levels are influenced by the autoimmune/inflammatory process and/or thyroid hormone status, using quantitative real-time PCR. Nine intact or fractionated adipose samples, from patients with GD and/or TED, were analysed ex vivo. Eight expressed the TSHR, at levels approaching the thyroid, and one was at the limit of detection. Thirteen/fifteen orbital and abdominal fat samples from patients free of GD and TED, measured ex vivo, were negative for TSHR transcripts and two were at the limit of detection. All preadipocyte samples induced to differentiate in vitro expressed the TSHR. To investigate the influence of thyroid hormone status on adipose TSHR expression, we induced hyper-and hypothyroidism in BALBc mice by administering tri-iodothyronine and propylthiouracil respectively. In euthyroid animals, whole fat samples were at the limit of detection and were not altered by thyroid hormone status. The results show that adipose TSHR expression ex vivo indicates adipogenesis in progress in vivo and is associated with the autoimmune/inflammatory process in GD and TED but is not restricted to the orbit or influenced by thyroid hormone status.

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