Intracellular cytokines in peripheral blood leucocytes in children with chronic renal failure.

We have previously shown that children with mild renal impairment show significant changes in leucocyte subsets and circulating cytokines, indicating that these patients show an increased inflammatory state. We hypothesised that measurement of intracellular cytokine production by lymphocytes and monocytes would more precisely define the immunological mechanism associated with the inflammatory state in children with pre-dialytic chronic renal failure. Blood was collected from children with chronic renal failure (CRF) who were not yet on dialysis and an age-matched control group. Leucocyte subsets and intracellular cytokine production were determined using flow cytometry. Children with CRF showed increased production of interleukin (IL)-12 by monocytes accompanied by decreased production of interferon (IFN)-gamma and increased production of IL-4 by T cells. There were no significant changes in the production of IL-8, IL-10, IL-6, IL-1alpha or tumour necrosis factor (TNF)-alpha by monocytes or in IL-2 or TNF-alpha production by T cells. There were no significant differences in total white cell count or lymphocyte count. There was a significant decrease in both B and NK cells. This study examines intracellular cytokine production in children with CRF in detail. It is the first to show that children with relatively mild renal failure display significant immunological changes of lymphocyte subsets and leucocyte cytokine production. These data provide a more accurate understanding of the immunological changes that may contribute to the clinical manifestations and progression of the disease.