Granulomas, focal accumulations of immune cells, form in the lung during Mycobacterium tuberculosis infection. Chemokines, chemotactic cytokines, are logical candidates for inducing migration of T lymphocytes and monocytes to and within the lung. TNF influences chemokine expression in some models. TNF-deficient mice infected with M. tuberculosis are highly susceptible to disease, and granuloma formation is inhibited. Through in vitro assays, we demonstrate that neutralization of TNF in M. tuberculosis-infected macrophages led to a reduction in many inflammatory chemokines, such as C-C chemokine ligand 5, CXC ligand 9 (CXCL9), and CXCL10. In TNF-deficient mice, immune cells migrated to the lungs early after infection, but did not organize to form granulomas within the lung. Although chemokine expression, as measured in whole lung tissue, was not different, the expression of chemokines in the CD11b+ subset of cells isolated ex vivo from the lungs of TNF-deficient mice had reduced expression of C-C chemokine ligand 5, CXCL9, and CXCL10 at early time points after TNF neutralization. Local expression of CXCR3-binding chemokines within the lungs, as determined by in situ hybridization, was also affected by TNF. Therefore, TNF affects the expression of chemokines by macrophages in vitro and CD11b+ cells in vivo, which probably influences the local chemokine gradients and granuloma formation.

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Weight loss improves health-related quality of life (HRQoL). However, regain after loss is common; little is known about the impact of weight regain on HRQoL in postmenopausal women. Woman on the Move through Activity and Nutrition (WOMAN) is a randomized lifestyle intervention trial of diet, physical activity, and weight loss in 508 postmenopausal women aged 52-62 years. This analysis focused on the women who lost ≥5 lb during the initial phase of the study, baseline to 6 months (n = 248). This cohort was divided into three groups based on subsequent weight change between 6 and 18 months: weight loss (WL; ≥5 lb loss), weight stable (WS; <±5 lb change), and weight regain (WR; ≥5 lb gain). HRQoL was measured at baseline, 6, and 18 months using the Short Form-36. Of the 248 women studied, 51 (21%) continued to lose weight after initial weight loss, while 127 (51%) maintained a stable weight, and 70 (28%) regained weight. Between baseline and 6 months, women in WR group had decreased mental health and socialfunctioning scores, while the WL and WS groups improved in these subscales. Between baseline and 18 months, energy improved most significantly in those with continued weight loss (P = 0.0003). Weight loss was correlated with a small to moderate improvement in perceived general health and energy, which was reversed by weight gain. Further study is needed to investigate the impact of a decline in mental health and social functioning on future weight regain.