OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings.

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Background:The type II C-type lectin CLEC4C inhibits IFN␣ production by plasmacytoid dendritic cells; its natural ligand is unknown. Results: Asialo-oligosaccharides with terminal residues of galactose bind CLEC4C and inhibit IFN␣ production. Conclusion: CLEC4C-mediated suppression of IFN␣ production is regulated by the masking/unmasking of galactose moieties. Significance: This represents a new potential strategy for regulating immune responses in pathological conditions.

The beneficial effects of hot springs have been known foreenturtes and treatments with sulphurous thermal waters are recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects of the therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements. Here, the effects of an S-based compound (NaSH) and of a specificsulphurous thermal water characterized by additional ions such as sodium chloride, bromine and iodine (STW) were investigated in terms of cytokine release and anti-oxidant enzyme activity in primary human monocytes and in saliva from 50 airway disease patients subjected to thermal treatments. In vitro, NaSH efficiently blocked the induction of pro-inflammatorycytokines and counterbalanced the formation of ROS. Despite STW not recapitulating these results, possibly due to the low concentration of S-based compounds reached at the minimum non-toxic dilution, we found that it enhanced the release of IL-10, a potent anti-inflammatory cytokine. Notably, higher levels of IL-10 were also observed in patients' saliva following STW treatment and this increase correlated positively with salivary catalase activity (r 2 =0.19, *p<0.01). To our knowledge, these results represent the first evidence suggesting that S-based compounds and STW may prove useful in facing chronic inflammatory and age-related illness due to combined anti-inflammatory and anti-oxidant properties.The beneficial effects of hot springs have been known for centuries. Treatment with sulphurous thennal waters has been recommended in a number of chronic pathologies as well as acute recurrent infections. However, the positive effects ofthe therapy are often evaluated in terms of subjective sense of wellbeing and symptomatic clinical improvements, while the effects of thermal waters on the immune, nervous and endocrine systems are still to be well elucidated. In addition, each different thermal water is unique in terms of composition and properties, and thus ad hoc studies may be required to elucidate its specific effects on cells and systems. In the last decade, numerous studies have been focused on understanding the molecular and cellular mechanisms involved in hot spring therapeutic effects (1). Besides the well documented effects on upper and lower respiratory airways, such as antibacterial and mucolytic activity

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