Elevated temperature regulates tumor necrosis factor-mediated immune killing.

The effect of elevated temperature (heat/fever) on the regulation of inflammatory processes was studied in an in vitro system. Since tumor necrosis factor (TNF), a central mediator in inflammation, is both a pyrogen and a cytokine capable of inducing the death of certain cells, we examined the relationship between heat shock and TNF-mediated immune killing. Heat shock of WEHI-164 fibrosarcoma cells significantly (and transiently) decreased the sensitivity of these cells to recombinant TNF-mediated lysis and to class II major histocompatibility complex-specific, TNF-secreting inflammatory T cell-mediated lysis. Incubating inflammatory T lymphocytes in elevated temperature transiently abolished their lytic potential and their ability to secrete TNF. Our data show that the pyrogen activity of TNF could control cytolytic processes during inflammation both by inducing protective protein(s) synthesis in target cells and by arresting TNF secretion by effector T lymphocytes.