Interleukin-10 (IL-10) and IL-12 are two cytokines secreted by monocytes/macrophages in response to bacterial products which have largely opposite effects on the immune system. IL-12 activates cytotoxicity and gamma interferon (IFN-␥) secretion by T cells and NK cells, whereas IL-10 inhibits these functions. In the present study, the capacities of gram-positive and gram-negative bacteria to induce IL-10 and IL-12 were compared. Monocytes from blood donors were stimulated with UV-killed bacteria from each of seven grampositive and seven gram-negative bacterial species representing both aerobic and anaerobic commensals and pathogens. Gram-positive bacteria induced much more IL-12 than did gram-negative bacteria (median, 3,500 versus 120 pg/ml at an optimal dose of 25 bacteria/cell; P < 0.001), whereas gram-negative bacteria preferentially stimulated secretion of IL-10 (650 versus 200 pg/ml; P < 0.001). Gram-positive species also induced stronger major histocompatibility complex class II-restricted IFN-␥ production in unfractionated blood mononuclear cells than did gram-negative species (12,000 versus 3,600 pg/ml; P < 0.001). The poor IL-12-inducing capacity of gram-negative bacteria was not remediated by addition of blocking anti-IL-10 antibodies to the cultures. No isolated bacterial component could be identified that mimicked the potent induction of IL-12 by whole gram-positive bacteria, whereas purified LPS induced IL-10. The results suggest that gram-positive bacteria induce a cytokine pattern that promotes Th1 effector functions.
Glycoconjugates containing the disaccharide unit GlcNAc beta 1 leads to 3Gal beta were suggested as receptors for pneumococci adhering to human pharyngeal epithelial cells. The receptor activity was detected both by inhibition of adhesion by an excess of free oligosaccharide and by induction or increase of adhesion after coating of target cells with glycolipid. Studies with free natural and synthetic oligosaccharides identified the disaccharide GlcNAc beta 1 leads to 3Gal beta as one critical binding site. The specificity of recognition was shown inter alia by the lack of inhibitory activity of GlcNAc beta 1 leads to 4Gal beta, which differs only in the linkage of the two sugars. Specific interference with pneumococcal adhesion by administration of soluble receptor sugar may improve our understanding of the role of adhesion in vivo.
Human milk inhibited the attachment of Streptococcus pneumoniae and Haemophilus influenzae to human pharyngeal or buccal epithelial cells. Infant formulas and cow and buffalo milk showed a lower inhibitory activity against pneumococci and enhanced the adhesion of H. influenzae. The antiadhesive effect against S. pneumoniae was found in both the high- and the low-molecular-weight fractions of milk. The inhibitory activity in the high-molecular-weight fraction was independent of specific antibody content; it was present after immunoadsorption and in the milk from IgA-deficient women. The inhibitory activity in the low-molecular-weight fraction was in part explained by the content of oligosaccharides corresponding to the carbohydrate moieties of the neolactoseries of glycolipids, which have previously been shown to act as receptors for attaching pneumococci. The antiadhesive activity against H. influenzae was restricted to the high-molecular-weight fraction of the milk and was unaffected by immunoadsorption. Milk may protect against otitis by reducing colonization.
Many breast cancer survivors have to deal with a variety of psychological and physiological sequelae including impaired immune responses. The primary purpose of this randomized controlled trial was to determine the efficacy of a mindfulness‐based stress reduction (MBSR) intervention for mood disorders in women with breast cancer. Secondary outcomes were symptom experience, health status, coping capacity, mindfulness, posttraumatic growth, and immune status. This RTC assigned 166 women with breast cancer to one of three groups: MBSR (8 weekly group sessions of MBSR), active controls (self‐instructing MBSR) and non‐MBSR. The primary outcome measure was the Hospital Anxiety and Depression Scale. Secondary outcome measures were: Memorial Symptom Assessment Scale, SF‐36, Sense of Coherence, Five Facets of Mindfulness Questionnaire, and Posttraumatic Growth Index. Blood samples were analyzed using flow cytometry for NK‐cell activity (FANKIA) and lymphocyte phenotyping; concentrations of cytokines were determined in sera using commercial high sensitivity IL‐6 and IL‐8 ELISA (enzyme‐linked immunosorbent assay) kits. Results provide evidence for beneficial effects of MBSR on psychological and biological responses. Women in the MBSR group experienced significant improvements in depression scores, with a mean pre‐MBSR HAD‐score of 4.3 and post‐MBSR score of 3.3 (P = 0.001), and compared to non‐MBSR (P = 0.015). Significant improvements on scores for distress, symptom burden, and mental health were also observed. Furthermore, MBSR facilitated coping capacity as well as mindfulness and posttraumatic growth. Significant benefits in immune response within the MBSR group and between groups were observed. MBSR have potential for alleviating depression, symptom experience, and for enhancing coping capacity, mindfulness and posttraumatic growth, which may improve breast cancer survivorship. MBSR also led to beneficial effect on immune function; the clinical implications of this finding merit further research.
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