Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cell activity in mice

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Abstract
Natural killer (NK) cells have an important role in non-adaptative resistance to tumours and their metastatic spread in vivo1–5. Maturation of NK cells and the intensity of their activity are affected by many endogenous and external factors, as well as by regulatory cells1. The possibility that some effects of the central nervous system on tumour resistance are mediated via NK activity has also been suggested6. Destruction of the tuberoinfundibular region of the hypothalamus in rodents led to a significant increase in tumour growth7–9. We show here that destruction of its ventromedial, dorsomedial and arcuate nuclei persistently abrogates NK activity in mice. By contrast, cortical lesion and operative stress depress it partially, and for a brief period only. Abrogation is the result of a block of NK lineage maturation, causing a severe decrease in the number of large granular lymphocytes (LGL), a lymphocyte population associated with NK activity10,11. Macrophage, B- and T-lymphocyte functions, however, are not significantly affected. Agents inducing NK-cell maturation or activation such as poly inosinic-polycytidylic acid (poly(I:C), interferon (IFN) and interleukin-2 (IL-2) restore NK activity, and normalize the number of LGL.