Th-17 cytokines and interstitial lung involvement in systemic sclerosis.

The two phenotypes of both limited and diffuse systemic sclerosis (SSc) have different forms of pulmonary involvement: pulmonary arterial hypertension (limited phenotype) or interstitial lung disease (ILD) (diffuse phenotype). We aimed to investigate whether Th17-related cytokines, as measured in exhaled breath condensate (EBC) and in serum were connected to ILD in diffuse SSc patients. We found that for both limited and diffuse SSc, the EBC levels of all cytokines and most of the cytokine serum levels were significantly higher in patients than in controls, while, the EBC levels of Th-17 cytokines and the serum levels of IL-10 and TNF-α were significantly higher in diffuse than in limited SSc. Moreover, the thoracic CT-scan score of ILD was significantly associated with the EBC levels of IL-1 beta and with the serum IL-23, TNF-α and IL-10 levels, whereas lung carbon monoxide diffusing capacity was negatively related to the EBC levels of IL-1 beta, IL-17 and serum IL-10. Serum IL-23 was also inversely correlated with vital capacity. In conclusion, in diffuse SSc patients our results show a clear link between Th-17 cytokines measured both in EBC and in serum with interstitial lung involvement. This highlights how important it is to target Th-17 cytokines when developing new treatments for lung fibrosis.

Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study.

L-carnitine was studied in forty-four men with stable chronic angina in a multicenter, double-blind, randomized, placebo controlled crossover trial. A cycloergometer exercise test was performed after a 10-day wash-out with placebo and at the end of each 4-week treatment period with either L-carnitine (1 g twice daily) or placebo. The mean (+/- SD) exercise work load showed an increase after L-carnitine compared to placebo (102.73 +/- 22.23 and 97.05 +/- 22.77 watts respectively, p = 0.001), as did the watts to onset of angina (95.7 +/- 24.07 and 87.44 +/- 24.67, p = 0.000). On the contrary, the ST segment depression was reduced by L-carnitine compared to placebo both at the maximum work load (1.40 +/- 0.90 and 1.69 +/- 0.82 mm, p = 0.05) and at the maximum work load common to L-carnitine and placebo (1.24 +/- 0.90 and 1.66 +/- 0.79 mm, p = 0.005). 22.7% of the patients became free of angina with L-carnitine and 9.1% with placebo. Resting and exercise blood pressure, heart-rate and double product were unaffected by L-carnitine. 1 patient decided to discontinue the trial because of gastric pyrosis while taking the active drug. The results of this study show that treatment with L-carnitine increases exercise tolerance and reduces ECG indices of ischemia in stable effort-induced angina.