Protein hormones and immunity

Abstract

A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid-stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and endocrine hormones.

Figure 1

A newly-discovered regulatory system between the endocrine and immune systems. Hormone and immune system crosstalk can antagonize the biological functions of hormones and cause endocrine resistance, which ultimately affects human health and well-being. During health, there is an absence of inflammation and an optimal balance of hormones and pro-inflammatory cytokines. The adrenal steroid glucocorticoid hormones act in many peripheral tissues to inhibit synthesis and action of proinflammatory cytokines. This balance is disrupted during inflammatory states in both the periphery and the brain. One mechanism by which this occurs is at the cellular level, whereby proinflammatory cytokines antagonize receptor-signaling pathways in muscle, brain and cancer cells. The body often responds by producing more hormones to overcome this cytokine-induced endocrine resistance. In this way, the endocrine-immune system communication pathway is reciprocal because the rise in concentration of hormones increases the hormone/cytokine ratio. This rise in the amount of hormone relative to cytokine partially overcomes the suppressive actions of both glucocorticoids and proinflammatory cytokines. This scenario even occurs in the brain, as demonstrated by abrogation of TNFα-induced sickness behavior following central administration of IGF-I.