Potentiation of interleukin-1beta adjuvant effects on the humoral immune response to antigen in adrenalectomized mice.
OBJECTIVE
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-1beta (rhIL-1beta) and at the same time immunized with 100 microg 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-1beta 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-1beta-treated animals, and again, further potentiated in ADX animals. Interestingly, while hrIL-1beta 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.
Kusnecov
A W
AW
Department of Psychology, Biopsychology and Behavioral Neuroscience Program, Rutgers University, Piscataway, NJ 08855, USA. kusnecov@rci.rutgers.edu
Rossi-George
A
A
D000315:Adrenalectomy; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D010047:Ovalbumin