Potentiation of Interleukin-1β Adjuvant Effects on the Humoral Immune Response to Antigen in Adrenalectomized Mice

Abstract

Objectives: Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a primary effect of interleukin-1 (IL-1), with elevated glucocorticoids considered a mechanism for negative feedback immunoregulation. However, there is little direct evidence of such a functional relationship between IL-1-mediated immunoregulation and neuroendocrine influences elicited by IL-1. Therefore, the goal of this study was to examine whether the known adjuvant effects of IL-1 are altered in the absence of neuroendocrine feedback due to adrenalectomy. Methods: Male BALB/c mice subjected to adrenalectomy (ADX) or sham surgery were administered with saline or recombinant human IL-1β (rhIL-1β) and at the same time immunized with 100 µg ovalbumin (OVA). In vivo and in vitro measures of antigen-specific IgG antibody production, IL-6 production and spleen cell proliferation were taken 6 and 12 days later. Results: It was demonstrated that administration of rhIL-1β at a dose that activates the HPA axis resulted in a significant augmentation of serum anti- OVA IgG antibody levels. Interestingly, this augmentation was potentiated in ADX animals. In addition, the in vitro spleen cell memory IgG antibody response to OVA was significantly augmented in rhIL-1β-treated animals, and again, further potentiated in ADX animals. Interestingly, while hrIL-1β treatment augmented antigen-stimulated IL-6 production – suggesting an effect of IL-1 on antigen-specific T helper 2 cell memory formation – potentiation was not evident in ADX animals. Conclusions: These results are consistent with the concept of HPA axis-mediated neuroendocrine feedback on excessive immune responsiveness due to IL-1. Such feedback may prevent disturbances to the self-limiting functions of the immune system, which are important to the prevention of autoimmune diseases, some of which involve elevated IL-1 production.