MODULATION OF THE IMMUNE SYSTEM BY HYPERTHERMIA

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While at the experimental stage, whole body hyperthermia (WBH) and other hyperthermia modalities are rapidly developing as methods of treating cancer. Considerable evidence has been generated showing that elevated temperature can cause dramatic changes on various components and functions of the immune system. We have shown that whole body thermogenic microwave (WBTMW) exposure stimulates macrophage (MP) functions, decreases natural killer (NK) activity, and depresses certain T cell populations. These diverse immune responses to WBTMW exposure leads us to propose that elevated temperature alters some fundamental immunoregulatory process(es) of the host. We have observed that WBTMW exposure markedly augments the primary (1 degree) and secondary (2 degree) IgM response of B cells to SRBC in both hamsters and mice. We will extend these studies and examine 1 degree and 2 degree IgG responses in WBH exposed mice to determine if there is any change in the ability of B cells to undergo Ig class switching. Since the B cell Ig response is regulated by MP and T cells, as well as NK cells, any or all of these populations could be implicated in the observed WBTMW effect on the Ig response. This proposal will also focus on experiments designed to examine the possibility of WBH-induced modulation of distribution and function of these various lymphocytes and monocytes. Employing monoclonal antibodies to T/H (Lyt 1), T/S (Lyt 2), NK (a-silo GM1) and B (Ig) cells in conjunction with fluorescense activated flow cytometry we will analyze the number of these cells in the spleens of WBH and control mice before and after immunization with SRBC. Ia antigen expression on MP can similarly be quantitated. Function changes in these cell populations will be quantitated by cell depletion and reconstitution experiments employing the panning technique with surface phenotypic specific monoclonal antibodies. B cell responses generated to these reconstituted WBH/control spleen cells will be measured in vitro by the Mishell Dutton technique or in vivo by implanting diffusion chambers into X- irradiated syngeneic mice. These experiments will quantitatively define potential influences of WBH treatment on T/H, T/S, MP, NK, and B cells on all phases of the PFC responses to SRBC. This proposal represents the first comprehensive analysis of potential WBH effects on the immunoregulatory work and will provide baseline data useful in the design of WBH multi-modality approaches to cancer treatment.