This study investigates acute (12 h) and long-term (13 days) effects of antigen challenge on hypothalamic-pituitary-adrenal (HPA) axis activation. Male rats were injected with phosphocholine-keyhole limpet hemocyanin (PC-KLH); immunoglobulin M levels were followed as an indication of lymphocyte stimulation, whereas changes in the activity of the HPA axis were examined by measuring plasma ACTH and corticosterone levels. Our results indicated that a moderate dose of PC-KLH antigen (75 μg) yielded a robust anti-PC-KLH antibody response (peaking at days 5-7) in the absence of changes in ACTH and corticosterone secretion. A 3-fold increase in antigen dose (225 μg) induced a small increase in corticosterone on day 5 that appeared to correlate with the peak anti-PC-KLH response. In contrast, injection of inter-leukin-lβ, lipopolysaccharides, or Newcastle disease virus caused acute increases in ACTH and corticosterone levels. As moderate doses of the antigen, PC-KLH, failed to induce detectable changes in the HPA axis while causing a strong antibody response, our results support the idea that HPA activation is not an obligatory step in the neuroimmune cascade after immune challenge. We conclude that HPA stimulation via immune modulation depends, in part, upon the form and strength of immune challenge. Certain antigen-driven responses may bypass HPA stimulation which could play an important role in B and T lymphocyte immunity to foreign antigens.
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