Suppressive effects of central opioids on delayed type hypersensitivity to trinitrochlorobenzene: comparative study with morphine and electroacupuncture

We reported previously that electroacupuncture (Acu) applied to the acu-point equivalent to GV4 in the mouse just before the 2,4,6-trinitrochlorobenzene (TNCB) challenge suppressed the delayed type hypersensitivity (DTH) through endogenous opioidergic systems in the brain, and the pituitary was pivotal in this immunosuppression. The purpose of the present study was to compare the suppressive effects of Acu with those of single, acute doses of morphine on TNCB-DTH in intact and hypophysectomized (HPX) mice. Subcutaneous morphine 10 mg/kg in ddY mice, 30 mg/kg in BALB/c mice or intracisternal morphine 40 micrograms/mouse in BALB/c mice given just before TNCB challenge suppressed (40-53%) the maximal extent of ear swelling at 24 hrs after challenge in intact mice. In HPX mice, the suppressive effects of intracisternal morphine 10 and 100 micrograms/mouse were less pronounced than those observed in intact mice and there was no significant difference between intact and HPX groups. In addition, suppressive effects observed with Acu or subcutaneous morphine (30 mg/kg) were effectively antagonized by pretreatment with intracisternal naloxone at a dose of as low as 2 micrograms/mouse. Naloxone alone had no effect of its own. These results suggest that 1) the activation of opioid receptor-mediated pathways in the brain, which occurs when opioids are endogenously released (Acu) or exogenously given (morphine), is important in the suppression of TNCB-induced DTH, a cell-mediated immune response, and 2) the pituitary is less pivotal in the suppressive effects of acute morphine than in those of Acu.