Patients with type 1 diabetes mellitus have impaired IL-1ß production in response to Mycobacterium tuberculosis.

Patients with diabetes mellitus have an increased risk of developing tuberculosis. Although the underlying mechanism is unclear, evidence suggests a role for chronic hyperglycaemia. We examined the influence of hyperglycaemia on Mycobacterium tuberculosis-induced cytokine responses in patients with type 1 diabetes mellitus (T1D). Peripheral blood mononuclear cells (PBMCs) from 24 male T1D patients with sub-optimal glucose control [HbA1c > 7.0% (53 mmol/L)] and from 24 age-matched male healthy controls were stimulated with M. tuberculosis lysate. Cytokine analysis, assessment of aerobic glycolysis, receptor recognition and serum cross-over experiments were performed to explore the mechanistic differences. PBMCs from T1D patients produced less bioactive interleukin (IL)-1ß in response to M. tuberculosis. IL-6 and interferon (IFN)-γ production trended towards a decrease, whilst other cytokines such as tumour necrosis factor (TNF)-α, IL-17 and IL-1Ra were normal. The decrease in cytokine production was not correlated to HbA1c or plasma glucose levels. Cross-over serum experiments did not alter the cytokine profile of T1D or control patients, arguing for an intrinsic cellular defect. Cellular metabolism and the expression of M. tuberculosis-related pattern recognition receptors (PRRs) such as TLR2, TLR4 and NOD2 did not differ between T1D patients and healthy controls. Compared to matched controls, T1D patients have a reduced capacity to produce pro-inflammatory cytokines in response to M. tuberculosis. The impaired IL-1ß production in T1D patients may contribute to the increased susceptibility to tuberculosis. This effect appears not to be related to prevailing glucose levels but to an intrinsic cellular deficit.

[Cheyne-Stokes respiration in patients with chronic heart failure: only a diagnostic marker or also a cardiovascular risk factor?]. / Cheyne-Stokes-Atmung bei Patienten mit chronischer Herzinsuffizienz: nur diagnostischer "Marker" oder auch kardialer Risikofaktor?

Sleep disordered breathing with predominant obstructive or central apnea is an under-recognized but highly prevalent comorbidity in patients with chronic heart failure. As the severity of heart failure increases the prevalence of central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) is also much more frequent. Cheyne-Stokes respiration is characterized by alternating periods of crescendo and decrescendo respiration followed by central apnea. Present data indicate that CSA-CSR is not only a compensatory response to severe heart failure but also a predictor of worse prognosis. However the results on long-term mortality are not consistent. The prognostic importance of night- and daytime CSR has to be further elucidated. Increased sympathetic nervous activity has been proposed to play a mayor role concerning progression and outcome of chronic heart failure by CSA-CSR.

Tumour necrosis factor-alpha increases intracellular Ca2+ and induces a depolarization in cultured astroglial cells.

Tumour necrosis factor (TNF)-alpha, a strong immune mediator, is released within the brain during inflammatory diseases and contributes to immunological activation of glial cells. Here we report that, in astrocytes, TNF-alpha also affects the intracellular Ca2+ homeostasis and basic electrophysiological properties such as the membrane potential. Using the Ca2+ indicator dye fura-2 in a cell culture model, we found that TNF-alpha (10-1000 U ml-1), but not interleukin 1 or 6, induced a slow but more than two-fold increase of the intracellular Ca2+ concentration, which could be blocked by Co2+ (1.0 mM), verapamil (100 microM) or omission of external Ca2+. This intracellular Ca2+ increase was accompanied by a marked decrease of the membrane potential by 35 mV. CSF of patients with bacterial meningitis, known to contain large amounts of TNF-alpha, induced a similar depolarization of astrocytes, which was markedly reduced by a neutralizing anti-TNF-alpha antibody. We conclude that TNF-alpha induces an increase of intracellular Ca2+ and a depolarization in astrocytes with the consequence of disturbing voltage-dependent glial functions such as regulation of local ion concentrations and glutamate uptake. During inflammatory CNS diseases this immuno-electrical coupling may contribute to an impairment of neuronal function.