Inflammation

Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury. Thiel, M. et al. PLoS Biol. 3, e174 (2005)

This study looks at the clinical implications of a recently described hypoxia-driven anti-inflammatory mechanism for patients with acute respiratory distress syndrome (ARDS) who are treated by mechanical ventilation with high oxygen concentrations. In several models, accumulation of adenosine in hypoxic conditions induces a physiological tissue-protective pathway through adenosine receptors (A2ARs). The authors confirm that oxygenation can exacerbate inflammatory lung damage by blocking the A2AR pathway in several in vivo mouse models of lung disease. Lung inflammation could be prevented by the addition of an A2AR agonist. They suggest that ventilation of patients with ARDS can cause an iatrogenic exacerbation of lung inflammation that could be treated with A2AR agonists or other anti-inflammatory drugs.

Immune regulation

Negative feed back regulation of T helper type 1 (TH1)/TH2 cytokine balance via dendritic cell and natural killer T cell interactions. Minami, K. et al. Blood 10 May 2005 (10.1182/blood-2004-12-4738)

This study describes how interactions between dendritic cells (DCs) and natural killer T (NKT) cells can regulate the T helper 1 (TH1)/TH2-cytokine balance. DCs can stimulate NKT cells by CD1d-restricted presentation of α-galactosylceramide (α-GalCer), but the NKT-cell response seems to be influenced by extracellular stimuli received by the DC. Indeed, pretreatment of α-GalCer-loaded DCs with TH1 or TH2 cytokines in vitro led to increased NKT-cell production of TH2 or TH1 cytokines, respectively, indicating that the NKT cells might provide a negative-feedback mechanism to maintain the cytokine balance. α-GalCer has been shown to have antitumour effects that require NKT-cell production of interferon-γ. So, by pretreating tumour-bearing mice with a TH2 cytokine, interleukin-4, the authors could enhance the α-GalCer-induced antitumour response and reduce tumour metastases.

Autoimmunity

Initiation and exacerbation of autoimmune demyelination of the central nervous system via virus-induced molecular mimicry: implications for the pathogenesis of multiple sclerosis. Croxford, J. L. et al. J. Virol. 79, 8581–8590 (2005)

Viral infections are suspected of triggering various autoimmune diseases, but proving this has proved controversial. This study shows that infection with a non-pathogenic variant of Theiler's murine encephalomyelitis virus (TMEV) expressing a Haemophilus influenzae-encoded peptide that mimics a self-myelin epitope induces and exacerbates disease in a mouse model of multiple sclerosis. The disease is mediated by cross-activation of autoreactive T cells and was shown to depend on processing of the mimic from the native H. influenzae protein and on virus-activated innate immune signals.