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

Natural killer (NK) cells have an important role in non-adaptative resistance to tumours and their metastatic spread in vivo^1-5. 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 growth^7-9. 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 activity^10,11. 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.