Interleukin (IL)-2-induced microvascular lung injury is an experimental paradigm commonly used to investigate the pathogenesis of the adult respiratory distress syndrome. Since tumor necrosis factor-alpha (TNF-alpha) is known to induce such an injury in vivo and since TNF-alpha is involved in other models of lung injury, we postulated that it might also mediate pulmonary toxicity after IL-2 administration. The present study tested this hypothesis by evaluating the effect of TNF-alpha inhibition on IL-2-induced lung injury in the rat. Recombinant human IL-2 (10(6) U IV per rat, n = 6) elevated lung water, myeloperoxidase activity, and protein accumulation in bronchoalveolar lavage fluid and induced tissue hypoxia. Also, IL-2 enhanced lung tissue TNF-alpha mRNA and peptide (1543 +/- 496 pg/g lung wet weight) localized to alveolar macrophages by in situ hybridization. In marked contrast, IL-2 failed to affect serum TNF-alpha, which remained at undetectable levels. Pretreatment with anti-TNF-alpha monoclonal antibody (25 mg/kg IV, n = 7) or the TNF-alpha synthesis inhibitor rolipram (200 micrograms/kg IV, n = 7) attenuated lung injury and reverted tissue hypoxia. Furthermore, TNF-alpha inhibition prevented the upregulation of lung tissue IL-1 beta, IL-6, cytokine-induced neutrophil chemoattractant, and E-selectin (ELAM-1) but not intercellular adhesion molecule-1 mRNAs in response to IL-2. These data imply that locally produced TNF-alpha mediates IL-2-induced lung inflammation and tissue injury and point to the potential utilization of TNF-alpha inhibitors in treating the pulmonary toxicity of IL-2 immunotherapy.

a b s t r a c tBackground: Cardiovascular risk in psoriasis (PS) appears to be dependent on disease severity. Circulating endothelial cell (CEC) counts appear to be elevated in numerous conditions associated with endothelial dysfunction including chronic immune-mediated inflammatory disorders. Adipokines could serve as a missing link between PS and comorbidities Aim: To evaluate the numbers of CECs and serum visfatin levels in PS patients in comparison to controls to investigate their possible role in increased cardiovascular disease (CVD) risk. Methods: Twenty-five PS patients and 15 healthy individuals were recruited. CECs numbers were detected in peripheral blood samples through studying CD146 and CD45 expression by flow cytometry. Serum visfatin levels were detected by enzyme-linked immunosorbent assay. Results: There was a statistically significant increase in CEC numbers and serum visfatin levels in PS patients compared to controls (p < 0.001) with significant positive correlations between serum visfatin levels and PS severity and numbers of CECs in PS patients. Also, there was a significant difference in numbers of CECs (p 0.001) and serum visfatin levels (p 0.001) between CVD risk positive and CVD risk negative psoriasis patients. Conclusion: Both numbers of CECs and serum visfatin levels were increased in PS patients compared with controls and also increased in CVD risk positive when compared with CVD risk negative PS patients. Both correlated with disease severity suggesting the possibility of increased CVD risk in PS patients.

Background: Hypofractionated radiotherapy in early breast cancer yields equivalent or better outcome in terms of efficacy, toxicity, cosmesis and cost-effectiveness. However, its role in node-positive breast cancer is less clear. Aim: To compare between adjuvant conventional and hypofractionated radiotherapy in node-positive breast cancer. Methods: Prospective pilot study of 66 node-positive breast cancer patients recruited over 1 year in a single institution. Patients were randomized to receive adjuvant conventional radiotherapy 200 cGy x 25 fractions with 200 cGy x 5 fractions boost to the tumor bed in case of breast conservation (control arm) or hypofractionated radiotherapy 266 cGy x 16 fractions with 266 cGy x 4 fractions boost to the tumor bed in case of breast conservation (intervention arm). The end points were disease-free survival, cosmetic outcome, ipsilateral arm lymphedema and acute skin reactions. Results: Disease-free survival did not differ significantly between the two treatment arms (p = 0.6) and the 2-year diseasefree survival rate was 87% and 89% in the hypofractionated and conventional arms. The rate of excellent/good cosmetic score was higher in the hypofractionated arm than the conventional as rated by patients (71% vs. 46%, p = 0.182) and physicians (29% vs. 8%, p = 0.32). Hypofractionation, when compared to conventional fractionation, was associated with less arm lymphedema (22% vs. 40%, p = 0.149), dry desquamation (28% vs. 53%, p = 0.04), skin darkness (0% vs. 15%, p = 0.054) and wet desquamation (16% vs. 21%, p = 0.601). Conclusion: Hypofractionated adjuvant radiotherapy in node-positive breast cancer patients is equivalent to conventional fractionation as regards disease-free survival, cosmetic outcome and arm lymphedema with less early skin reactions.

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