title: Equianalgesic doses of subcutaneous but not intrathecal morphine alter phenotypic expression of cell surface markers and mitogen-induced proliferation in rat lymphocytes.
abstract: BACKGROUND
  Surgical trauma and opioids are linked with suppression of immune function. Evidence suggests a probable supraspinal action of morphine in altering immune function, although the role of spinal systems have not been evaluated. Therefore, this study compared the effect of equianalgesic doses of subcutaneous and intrathecal morphine on lymphocyte proliferative responses and phenotypic expression of lymphocyte cell surface markers in rats.
  
  
  METHODS
  Equianalgesic doses of subcutaneous (10 mg/kg) or intrathecal (30 micrograms, by a chronic intrathecal catheter) morphine were given twice for 5 h (time 0 and 2.5 h). Immediately after the 5-h period or 24 h after the initial injection, spleens were harvested and lymphocytes isolated. Mitogen-induced (phytohemagglutinin, concanavalin A, pokeweed, lipopolysaccharide) lymphocyte proliferation and monoclonal antibody labeling of cell surface markers (T cell, B cell, CD4+, CD8+) were then performed.
  
  
  RESULTS
  Subcutaneous morphine acutely suppressed lymphocyte proliferation to the mitogens phytohemagglutinin, pokeweed, and concanavalin A by 37%, 21%, and 20% respectively; however, proliferative responses returned to baseline within 24 h. Morphine treatment did not alter the response to lipopolysaccharide. The number of splenic lymphocytes also decreased, whereas the percentage of lymphocytes expressing the CD4+ marker (T helper/inducer cells) modestly increased. Intrathecal morphine did not alter lymphocyte proliferative responses, nor did it change phenotypic expression of cell surface markers.
  
  
  CONCLUSIONS
  Subcutaneous morphine inhibited lymphocyte proliferation, decreased splenic lymphocyte number, and altered phenotypic expression of cell surface markers, whereas equianalgesic doses of intrathecal morphine did not. Although these results suggest that spinal opioids may have theoretical benefits for the analgesic management of immunocompromised patients, further studies are clearly indicated.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Hamra
authors.forename: T L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001794:Blood Pressure / Q000187:drug effects; D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D002245:Carbon Dioxide / Q000097:blood; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010313:Partial Pressure; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013810:Therapeutic Equivalency
chemical_list: D000701:Analgesics, Opioid; D015704:CD4 Antigens; D016827:CD8 Antigens; D008934:Mitogens; D002245:Carbon Dioxide; D009020:Morphine