Cytokine and lymphocyte activation during experimental acute pyelonephritis.

We studied the cellular and humoral events which follow experimental acute pyelonephritis from P-fimbriated Escherichia coli to gain insight into the relationships among cells and specifically cytokines to determine how early events in untreated infection lead to renal damage. Cynomolgus (Macaca fascicularis) monkeys were studied after they were subjected to unilateral ureteral bacterial inoculation. We evaluated the blood for leukocytosis and studied lymphocyte subsets using flow cytometry and monoclonal antibodies to the subsets and serum, complement, cytokines and antibody titers. Interleukin-1, 2 and 6 and tumor necrosis factor (TNF) were assayed by enzyme-linked immunoadsorbent assay (ELISA), using monoclonal and polyclonal antibodies. Leukocytosis was marked and there were significant elevations in serum cytokines, interleukin-1 alpha, 2 and 6 with only small changes in the level of TNF. Interleukin-2 levels were sustained and may have upregulated the homing receptor for virgin lymphocytes. The studies illustrated the unique relationship between cytokines and lymphocytes and the response to bacterial infection, showing that the inflammatory response is regulated not only by cytokine activity but also by lymphocyte activation.