SYNERGISTIC INDUCTION OF THERMOTOLERANCE IN MURINE NATURAL-KILLER-CELLS BY INTERFERON-ALPHA AND MILD HEAT-SHOCK

Splenic lymphocytes from C3H/HeN mice were primed in vivo or in vitro with the interferon inducer poly inosine:cytosine (Poly I:C) or in vit ro with interferon alpha (IFN alpha) and evaluated for their natural k iller (NK) activity after exposure to hyperthermia for defined periods . Lytic activity against cells of the NK-susceptible Moloney lymphoma cell line YAC by Poly I:C- or IFN alpha-primed spleen cells exhibited thermotolerance to 41, 42 and 43 degrees C exposure compared to unprim ed cells. Spleen cells were also incubated for 1 h at 40 or 37 degrees C prior to exposure to 42 degrees C. Incubation at 40 degrees C produ ced a modest increase in thermal resistance to 42 degrees C by otherwi se unprimed spleen cells. Spleen cells that had been primed by Poly I: C or IFN alpha followed by 1 h at 40 degrees C were rendered even more resistant to hyperthermia at 42 degrees C. These data suggest that tw o host responses to viral infection, fever and production of IFN alpha , may endow cells involved in the inflammatory response (in this case NK cells) with resistance to more severe stress. Further, IFN alpha an d fever may synergize in this protective mechanism.