INFLUENCE OF ELEVATED-TEMPERATURE ON NATURAL-KILLER-CELL ACTIVITY, LYMPHOKINE-ACTIVATED KILLER-CELL ACTIVITY AND LECTIN-DEPENDENT CYTOTOXICITY OF HUMAN UMBILICAL-CORD BLOOD AND ADULT-BLOOD CELLS

Purpose: To determine whether hyperthermia is to the benefit or detrim ent of host immune function, the effect of hyperthermia was evaluated on various functions of T-lymphocytes from human umbilical cord blood and compared to that of adult blood. Methods and Materials: Nonadheren t mononuclear cells from cord blood or adult blood were used as the ef fector cells. To generate lymphokine activated killer (LAK) cells, eff ector cells were kept in culture for 5 days in complete medium contain ing recombinant human interleukin-2. To activate effector cells to bec ome cytotoxic, cells were kept in culture in complete medium containin g Con A. Cytotoxicity was determined in a standard 4-h chromium releas e assay using K-562 human erythroleukemic cells (in the natural killer cell activity assay) or Daudi cells (in the LAK cell activity or Lect in dependent cytotoxicity assay) as targets. For heat effects, cells i n complete medium were heated at the desired temperature in a water ba th for 1 h. Results: Lymphokine-activated killer cell activity, lectin -dependent cytotoxicity and T-cell proliferative capacity were not def icient in human cord blood. Cytotoxic activities of T-cells from adult blood as well as from cord blood can be enhanced at febrile range (le ss than or equal to 40 degrees C), and were significantly decreased by exposure to 1 h at 42 degrees C. Conclusion: The febrile responses (l ess than or equal to 40 degrees C) to infection, in the course of mali gnant disease and with biological response modifiers treatment, may al l be related to host defense mechanisms. Based on these observations, whole body hyperthermia (less than or equal to 40 degrees C), in combi nation with the appropriate cytokines, may have therapeutic potential in the treatment of neonatal infections and malignancies under certain circumstances. Hyperthermia in febrile range may, therefore, confer a n important immunoregulatory advantage to the host. In contrast, tumor killing therapeutic temperature (> 42 degrees C) which inhibits host immunocompetence should probably be used only for local hyperthermia.