Brown adipose tissue. Its in vivo immunology and involvement in neuroimmunomodulation

The material presented here summarizes the bulk of the presently available immunologic data bearing upon the in vivo relationship between brown adipose tissue and the immune system. The experiments were carried out in rats adipectomized (by surgical excision of the interscapular brown adipose tissue at birth), thymectomized (by neonatal removal of the thymus), adipectomized and thymectomized, and corresponding sham-operated controls. The following immune phenomena were studied: antibody production to soluble and corpuscular antigens; Arthus and delayed hypersensitivity skin reactions to bovine serum albumin; rejection of allogeneic skin and thyroid grafts; lymph node enlargement in a host-versus-graft reaction; experimental allergic encephalomyelitis and thyroiditis; immune response in normal animals treated with extracts from brown adipose tissue; allergic encephalomyelitis in thymoadipectomized animals; plaque-forming cell response and hemagglutinating antibody titers in animals injected with met-enkephalin and leu-enkephalin; and survival rate of adipectomized mice inoculated with Sarcoma-I cells. The results indicated that the cell-mediated immune reactions were potentiated in adipectomized rats. Antibody production was not significantly changed by neonatal adipectomy. Adipectomized mice, inoculated with Sa-I tumor cells, survived longer than controls, thus indicating that adipectomy made possible the recognition of discrete histocompatible differences between Sa-I cells and A/JAX mice. Adipectomy increased the ability of rats to develop autoimmune diseases. Saline extracts from brown adipose tissue of newborn rats suppressed hypersensitivity skin reactions in normal adult rats. Thymoadipectomized rats showed an almost normal ability to develop allergic encephalomyelitis, a finding that suggested that the potentiating influence of adipectomy on encephalomyelitis was neutralized by thymectomy. It appears that brown adipose tissue functions as a natural antagonist of the thymus. Enkephalins were found to be more effective immunosuppressors in adipectomized than in normal animals. The last finding establishes a functional link between brown adipose tissue and neuropeptides. It seems that the potentiation of immune response in adipectomized animals is effected by altered release of yet unidentified mediators and modulators. The evidence indicates that brown adipose tissue, in which neurohumoral activity occurs, may be an important component of an integrated immunoneuroendocrine system.