Effects of growth hormone levels on the humoral immune response in mice with respect to gender and age

Growth hormone (GH) is a neuroendocrine protein that interacts with the immune system. The effects of GH levels on the humoral immune response were investigated in bovine GH-transgenic (Tg) mice (overexpress GH), Ames dwarf (Df) mice (GH-deficient) and respective normal (NTg and NDf) littermates (normal GH levels) with respect to gender and age. One-, two-, four- and six-month-old male and female mice were injected with either tetanus toxoid (TT) to induce specific antibody (Ab) production, or normal saline. Blood was collected prior to primary immunization, pre-secondary immunization (day 14), and at 21 and 28 days post-primary immunization (PPI) from all mice. Four-month-old mice were subjected to identical treatment and bled at 8, 12, 16, 20 and 24 weeks PPI. Plasma TT-specific Ab titers were determined by ELISA. Tg mice produced less Ab at all ages than age-matched NTg, Df or NDf mice at either 14, 21 or 28 days PPI (p < 0.05). Titers were highest at four months of age in all mice, peaked at 28 days PPI and declined gradually from 8 to 24 weeks PPI.;Peripheral lymphocytes were enumerated to identify mechanisms responsible for differences in Ab levels. Cytokines involved in Th1 and Th2 differentiation were measured by ELISA after in vitro lymphocyte stimulation with TT. Elevated corticosterone levels in the Tg animals were investigated as a possible humoral immunosuppressant mechanism. Adrenalectomies were performed on transgenic and control mice to decrease corticosterone prior to primary immunization. Plasma corticosterone levels were measured by RIA. CD4+ and CD8+ T cells were lower in Tg than NTg, Df or NDf (p < 0.01) and higher in Df than NDf (p < 0.04) mice. No differences were found in B cell numbers between Tg, NTg or Df mice. Th2 populations were greater in Tg and Df mice compared to NTg or NDf mice (p < 0.02). No differences were found in IL-4 or IFN-gamma levels between Tg and NTg mice. Ab production was not enhanced by decreasing corticosterone in Tg mice.;Thus, high endogenous GH levels inhibit specific Ab production and peripheral CD4+ and CD8+ T cell populations but not peripheral B cell numbers, Th2 populations or IL-4 production. Elevated corticosterone levels are not solely responsible for suppressed humoral immune responses. Low levels of endogenous GH do not affect specific Ab production but contribute to increased peripheral T cell numbers. Humoral immune responses appear optimum in these mice at four months of age and have no patterns of significant variation with respect to gender.