The molecular basis for bidirectional communication between the immune and neuroendocrine systems

IL-2 has analgesic effects in both central and peripheral nervous systems. There are two distinct domains in IL-2 molecule mediating immunologic and analgesic activity, respectively. The analgesic domain of IL-2 may be composed of the 44th Phe, 45th Tyr, 107th Tyr, and 117th Phe residues that are located closely in the tertiary structure of IL-2. The analgesic activity may be mediated through the analgesic domain interaction with opioid receptor. In addition to peptides, cytokines may directly bind to peptide receptors, other than their specific cytokine receptors themselves. Conversely, peptides may also interact with cytokine receptors. Thus, peptide neurotransmitters and hormones may serve as endogenous regulators of the immune system, and cytokines may also serve as neurotransmitters. Multiple actions might be mediated by interactions between distinct domains of bioactive molecules with different receptors.