Interactions between the nervous and immune systems have become a focus of attention for pathophysiology. Hormones of neural origin, particularly opioid peptides, are involved in the regulation of immune cell function. [Met5]-enkephalin (ME), an opioid peptide with a widespread distribution in the central nervous system and in peripheral tissues, has been implicated in a number of physiological and pathophysiological states involving neural and hormonal actions. Endogenous opioids such as ME, beta-endorphin are involved in neuronal modulation of immune function. ME acts via classical opioid receptors on human phagocytic leukocytes to increase the percentage of active T-rosettes to increase natural killer cell activity. It has also been shown by our previous work that ME and pro-enkephalin modulate mitogen-stiumlated splenic B-cell function. We have also reported that ME has very weak stimulatory effect on IL-1beta secretion from microglia in cultures, but it suppresses the LPS-induced expression of IL-1beta mRNA. The mechanism underlying this phenomena is still not clear. Currently, we are focusing on the possible modulatory influences of beta-endorphin, another opioid peptide, on microglial function. Preliminary work has been done on fetal mouse mixed brain cell cultures. Brain cells were cultured for two weeks before experimentation. Lipopolysaccharide (LPS) has been used in this study as a positive inflammatory agent. Our results showed that LPS concentration dependently increased the production and secretion of IL-1a, IL-1beta and IL-6 from mixed brain cell cultures. Naloxone, an opioid receptor antagonist, partially blocked the LPS-inducedrelease of IL-1beta and IL-6 from microglia in mixed culture. Beta-endorphin (10-14m to 10-6m) significantly suppressed the LPS-induced release of IL-1B from microglia in mixed cultures. These results suggest that beta-endorphin may regulate brain immune function during stressful conditions.
