Interleukin-2 regulatory effect on P-selectin and interleukin-8 production in patients with chronic renal failure

Patients with chronic renal failure (CRF) show a clinical state of immunodysfunction that occurs in both humoral and cellular immunity as well as inflammatory response. In this study, we investigated the mononuclear-endothelial cells (MCs/ECs) interaction and the possible protective role of IL-2 as the main T lymphocyte activator in CRF patients. The levels of soluble P-selectin (sP-selectin) and interleukin-8 (IL-8) as the two main mediators of MCs/ECs interaction were measured in IL-2 supplemented and non-supplemented peripheral blood mononuclear cells (PBMCs) supernatant of CRF patients. The obtained results were correlated with those of sex and age matched controls. Significantly higher levels of sP-selectin and IL-8 were detected in both IL-2 supplemented and non-supplemented PBMCs culture supernatant of CRF patients than controls (P = 0.000). Those levels were significantly lower in IL-2 supplemented PBMCs culture supernatant than non-supplemented ones of both CRF (P = 0.000) (for both mediators) and normal control groups (P = 0.01, P= 0.04 for sP-selectin and IL-8 respectively). The higher sP-selectin in CRF indicates impairment of MCs/ECs interaction that may be resulted from blockade of P-selectin receptors on PBMCs by P-selectin molecules shedded from ECs to plasma and bind to PBMCs in vivo. The elevated IL-8 level in PBMCs of CRF reflect the imbalance of Thl/Th2 ratio and subsequent impairment of cellular immunity in those patients. The lower level of both sP-selectin and IL-8 in IL-2 supplemented PBMCs supernatant than in non-supplemented one seemed to be due to the IL-2 induced proliferation of Th1 lymphocytes yielding newly in vitro formed T cells which do not carry P-selectin as well as relative increase of Th1/Th2 ratio in both normal and CRF groups. Thus, IL-2 may improve the MCs/ECs interaction and correct the Th1/Th2 ratio in CRF providing a novel promising therapeutic approach to improve the immuno-pathological condition of those patients.