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Tetanus Toxoid Stimulation of the Hypothalamic-Pituitary-Adrenal Axis Correlates Inversely with the Increase in Tetanus Toxoid Antibody Titers¹

Department of Medicine (E.O.), Channing Laboratories (D.L.K.), and the Endocrine-Hypertension Division, Department of Medicine (R.E.G., G.K.A.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Gail K. Adler, M.D., Ph.D., Endocrine-Hypertension Division, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115.

In humans, endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, and the resulting increase in cortisol modulates the immune response. There is little information on the HPA axis response to other antigens. We examined the effect of the protein antigen tetanus toxoid on HPA axis activity in 10 healthy, premenopausal women (aged 28.6 ± 2.6 yr). Subjects received im injections of placebo and tetanus toxoid at 1600 h on consecutive days. Blood samples for ACTH and cortisol were obtained every half-hour from -1 to 6 h and at 8, 12, and 16 h after each injection. Compared to placebo, tetanus toxoid administration stimulated significant increases in plasma ACTH and serum cortisol, with the maximum cortisol increase of 1.6-fold occurring 4.5 h after drug administration. Urinary free cortisol increased 1.8-fold in the 8 h after tetanus toxoid administration compared to that after placebo administration. Additionally, there was a significant inverse correlation (r = 0.87; P < 0.005) between the tetanus toxoid-induced increase in serum cortisol and the increase in tetanus antibody levels measured 1 month postvaccination. Thus, administration of the protein antigen tetanus toxoid activated the HPA axis in healthy, premenopausal women. This activation of the HPA axis correlated inversely with the antibody response to tetanus toxoid.