Opioids have been demonstrated to alter immune functions. The natural opioid peptide methionine enkephalin (Met-ENK) has been reported to boost T-lymphocyte numbers and function in a cytokine-like manner. Thus, this peptide has been suggested as an adjunct to antiviral chemotherapy in the treatment of acquired immunodeficiency syndrome (AIDS). The combination of antiviral and immunostimulatory substances has been under serious evaluation for effectiveness in treating AIDS for several years. However, this approach has been limited by the need to be conservative in designing clinical protocols. The current proposal uses a murine retrovirus-induced immunodeficiency model to study various combinations of the anti-retroviral drug azidothymidine and Met-ENK. Initial studies indicate that Met-ENK can significantly enhance protection against the mouse retrovirus infection, as measured by reduced splenomegaly and increased survival. The use of the murine model, which uses various numbers of subjects treated by drug combinations, is advantageous in allowing studies that fully evaluate the interaction between these agents. These studies will focus on determining: 1) the optimal drug combination in dosing, time, and route of administration; 2) whether or not the Met-ENK effects are via opioid receptors; 3) if the effects of Met-ENK result in a cytokine pattern (type I cytokines) that favors resistance to disease; and 4) whether therapy reduces viral load temporarily or long term, and whether viral infection is actually cleared from the mice. This model has excellent potential for establishing whether the therapeutic combination of antiviral and immunostimulatory agents may be applied in the future to human AIDS or other retroviral infections.
