Regulatory CD4+ T cells are important for the homeostasis of the immune system and their absence correlates with autoimmune disorders. Here, we investigate the capacity of IL-27, a cytokine with pro- and anti-inflammatory properties, to regulate the generation of transforming growth factor beta (TGFbeta)-inducible forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. Our results demonstrate that IL-27 inhibits the acquisition of the Treg phenotype at the level of Foxp3, CD25 and CTLA-4 (CD152) expression as well as the suppressive function. In contrast to TGFbeta-induced Treg cells, the cells generated after differentiation in the presence of TGFbeta and IL-27 maintained the ability for IL-2 and tumour necrosis factor alpha (TNFalpha) production. The inhibitory effect of IL-27 on Treg generation was at least partially signal transducer and activator of transcription 3 (STAT3) dependent as examined by targeted STAT3 protein inhibition using small interfering RNA (siRNA), while STAT1-dependent signals seemed to oppose the STAT3 signals. In turn, TGFbeta blocked IL-27-induced T(h)1 differentiation. Thus, IL-27 and TGFbeta mutually control their effects on CD4+ T-cell differentiation, whereby IL-27 favours inflammatory conditions through a STAT3-dependent inhibition of Treg generation.

The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of the innate host defense system at surfaces of the body. Besides its direct anti-microbial activity, the peptide interacts with different cell types. Dendritic cells (DCs) play a central role in mucosal host defense. It was the aim of the study to determine whether LL-37 modulates the response of DCs to pathogen-associated molecular patterns. Monocyte-derived DCs were stimulated with the Toll-like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured classical markers of DC maturation and assayed the ability of the DCs to activate T cell responses. Co-incubation with LL-37 resulted in suppressed activation of DCs. Levels of released IL-6, IL-12p70 and TNF-alpha and surface expression of HLA-DR, CD80, CD83, CD86 and the chemokine receptor CCR7 were decreased. Exposure of DCs to LL-37 during LPS exposure induced co-cultured naive T cells to produce less IL-2 and IFN-gamma and decreased their proliferation. The response of memory T cells to a recall antigen was also decreased. In conclusion, we demonstrate that the anti-microbial peptide LL-37 inhibits the activation of DCs by TLR ligands. We propose that LL-37 is a regulator of host defense responses at the intersection of innate and adaptive immune systems.

We report what is to the best of our knowledge the first case of persistent human listeriosis. A housewife underwent excision of a leiomyosarcoma and implantation of a prosthetic knee device. Infection of the device with Listeria monocytogenes occurred and persisted for 2 years. Despite having an allergy to ampicillin, the patient was cured solely by antibiotics and without surgery.

In order to assess if a mixture of phenylephrine/lignocaine is as effective as cocaine for local analgesia and vasoconstriction during nasal fibreoptic intubation, 99 patients receiving topical nasal analgesia either with cocaine 10% or a mixture of phenylephrine 1% and lignocaine 4% were studied in a randomized double-blind investigation. After topical analgesia a flexible fibreoptic endoscope was advanced through a nostril. Larynx, glottis and trachea were endoscopically sprayed with lignocaine. Following induction of anaesthesia a nasotracheal tube was inserted fibreoptically. Pain intensity and amount of epistaxis during endoscopy were assessed. Blood pressure, heart rate and ECG-ST segment were determined before and after topical nasal analgesia, after induction of anaesthesia and after nasotracheal intubation. There were no significant differences in pain intensity of epistaxis between groups during endoscopy, nor significant alterations in haemodynamic parameters or ST-segment. It is concluded that the mixture of phenylephrine and lignocaine is a useful alternative to cocaine for local analgesia and vasoconstriction during nasal fibreoptic intubation.