The opioid antagonist naloxone induces a shift from Type 2 to Type 1 cytokine pattern in BALB/cJ mice

Opioid peptides affect different immune functions. We present evidence that these effects could be mediated by the modulation of T(H)1/T(H)2 cytokine production. BALB/cJ mice were immunized with 50 or 100 mu g of the protein antigen keyhole-limpet hemocyanin (KLH), and treated acutely or chronically with the opioid antagonist naloxone, One and 2 weeks after immunization, t he production of cytokines by splenocytes was evaluated by in vitro restimu lation with KLH. The acute and chronic treatment with the opioid receptor a ntagonist naloxone decreased the production of interleukin (IL)-4 by spleno cytes of BALB/cJ mice, In contrast, IL-2 and interferon-gamma levels increa sed after naloxone treatment. Finally, the opioid antagonist diminished the serum immunoglobulin G anti-KLH anti-body titers, These results suggest th at naloxone increases T(H)1 and decreases T(H)2 cytokine production. The ef fect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could therefore activate TH2 and suppress TH1 cytokines. (C) 2000 by The American Society of Hematology.