Abstract
Backgrounds Many cases of patients with chronic renal failure (CRF) on hemodialysis are known to be infected with Staphylococcus aureus ( S. aureus) from the sites of blood vessel puncture for hemodialysis and the custody of the vascular access catheter. S. aureus produces superantigens, such as toxic shock syndrome toxin-1 (TSST-1), which may influence the sensitivity of peripheral-blood mononuclear cells (PBMCs) to immunosuppressive drugs after they are received postrenal transplantation. Methods We examined the drug-sensitivities of PBMCs stimulated with TSST-1 in 18 CRF patients on hemodialysis. PBMCs were isolated from venous blood before hemodialysis, and were cultured in the presence of concanavalin A (ConA) or TSST-1 and serial concentrations of the drugs. In vitro drug concentrations giving 50% inhibition (IC 50) of PBMC blastogenesis were calculated. INF-γ and IL-4 in supernatants of cultured PBMCs were measured with ELISA. Results The median (range) IC 50 values (ng/ml) for four drugs; tacrolimus, cyclosporine, methylprednisolone, and prednisolone, evaluated in ConA-stimulated PBMCs of CRF patients were 0.04 ng/ml (0.03–0.21), 3.0 (0.1–15.1), 3.0 (1–104), and 16.2 (5.9–35.4), respectively. The values for the four drugs evaluated in TSST-1-stimulated PBMCs were 0.22 (0.08–0.36), 18.9 (5.1–38.2), 328.3 (1.9–1000), and 150.9 (94.7–880), respectively, which were significantly higher than those evaluated in the ConA-stimulated PBMCs ( p = 0.003–0.023). Amounts of INF-γ and IL-4 produced from cells were not significantly different between the ConA-or TSST-1-stimulated PBMCs in the presence or absence of immunosuppressive drugs. Conclusion These observations raise the possibility that TSST-1 induced by S. aureus infection attenuates the clinical efficacy of glucocorticoids and calcineurin inhibitors in CRF patients after renal transplantation. Furthermore, INF-γ and IL-4 related pathways appear not to play major roles in the TSST-1-induced attenuation of the drug sensitivities.
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