Stress Applied during Primary Immunization Affects the Secondary Humoral Immune Response in the Rat: Involvement of Opioid Peptides

The effect of unpredictable, inescapable and uncontrollable electric tail shocks (ES) on the humoral immune response to bovine serum albumin (BSA) was investigated in the rat. Contributions of the procedures that accompany shock delivery, such as witnessing the ES procedure (stress witnessing, SW) and exposure to the apparatus for shock delivery (apparatus control, AC) to the changes in specific immunity induced by ES were also tested. All procedures were applied during primary and/or secondary immunization. It was demonstrated that exposure to ES during primary immunization with BSA significantly suppressed specific anti-BSA antibody production after secondary and tertiary immunization with the same antigen. Exposure to the SW procedure during primary immunization with BSA enhanced the specific antibody level after secondary immunization, while exposure to the apparatus alone did not influence the development of either the primary or secondary humoral immune response to BSA. Both ES-induced suppression and SW-induced potentiation of the humoral immune response were partially inhibited by prior treatment with the opioid receptor antagonist naloxone. Additionally, treatments with the opioid peptides methionine- and leucine-enkephalin decreased anti-BSA antibody level, mimicking to some extent the effects of ES. It is suggested that ES and endogenous opioid peptides had long-term effects on humoral immunity through mechanisms involving immunologic memory.