Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.

Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

Effect of calcitriol treatment on psoriasis in hemodialysis patient: a case report.

The case of a 67-year-old man who has had psoriasis with multiple joints involvement for 30 years and renal failure for 1 year is described. He was admitted because of uremic symptoms and exacerbation of psoriasis. Hypocalcemia and low serum active 1.25(OH)2D3 were also observed. Hemodialysis, oral 1.25(OH)2D3 and CaCO3 supplement were employed. Interestingly, the psoriasis strikingly improved. The relationships among psoriasis, renal failure, 1.25(OH)2D3, serum calcium level and dialysis are discussed.

Rapid correction of metabolic acidosis in chronic renal failure: effect on parathyroid hormone activity.

To investigate the effect of rapid correction of chronic metabolic acidosis on circulating intact parathyroid hormone (I-PTH) activity by free calcium clamp in chronic renal failure, 18 patients were enrolled in this study. Metabolic acidosis was corrected by continuous bicarbonate infusion while plasma ionized calcium was clamped at the preinfusion level throughout the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, serum total calcium and 1,25(OH)2 vitamin D3 levels increased significantly while serum concentrations of I-PTH, alkaline phosphatase and albumin showed significant decreases after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium and inorganic phosphorus levels showed no significant difference before and after bicarbonate infusion. These results demonstrate that rapid correction of metabolic acidosis attenuates circulating PTH activity in chronic renal failure and may underline the importance of maintaining normal acid-base homeostasis particularly in the presence of secondary hyperparathyroidism.