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 microg of the protein antigen keyhole-limpet hemocyanin (KLH), and treated acutely or chronically with the opioid antagonist naloxone. One and 2 weeks after immunization, the production of cytokines by splenocytes was evaluated by in vitro restimulation with KLH. The acute and chronic treatment with the opioid receptor antagonist naloxone decreased the production of interleukin (IL)-4 by splenocytes of BALB/cJ mice. In contrast, IL-2 and interferon-gamma levels increased after naloxone treatment. Finally, the opioid antagonist diminished the serum immunoglobulin G anti-KLH antibody titers. These results suggest that naloxone increases T(H)1 and decreases T(H)2 cytokine production. The effect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could therefore activate T(H)2 and suppress T(H)1 cytokines. (Blood. 2000;95:2031-2036)
Sacerdote
P
P
Department of Pharmacology, University of Milano, Milan, Italy. paola.sacerdote@unimi.it
Manfredi
B
B
Gaspani
L
L
Panerai
A E
AE
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006433:Hemocyanins / Q000276:immunology / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000906:Antibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D015847:Interleukin-4; D009270:Naloxone; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin