Abstract
Evidence indicates an intimate connection between the neuroendocrine and the immune systems. A number of in vitro and in vivo studies have demonstrated growth hormone (GH) involvement in immune regulation. The GH receptor is expressed by several leukocyte subpopulations, and GH modulates immune cell proliferation and activity. Here, we found that sustained GH expression protected against collagen-induced arthritis (CIA); in GH-transgenic C57BL/6 (GHTg) mice, disease onset was delayed, and its overall severity was decreased. The anti-collagen response was impaired in these mice, as were inflammatory cytokine levels. Compared to control arthritic littermates, immunized GHTg mice showed significantly lower RORγt (retinoic acid receptor-related orphan receptor gamma 2), IL-17, GM-CSF, IL-22, and IFNγ mRNA expression in draining lymph nodes, whereas there were no differences in IL-21, IL-6, or IL-2 mRNA levels. Data thus suggest that Th17/Th1 cell plasticity toward a pathological phenotype is reduced in these mice. Exogenous GH administration in arthritic DBA/1J mice reduced the severity of established CIA as well as the inflammatory environment, which also shows a GH effect on arthritis progression. These results indicate that GH prevents inflammatory joint destruction in CIA. Our findings demonstrate a modulatory GH role in immune system function that contributes to alleviating CIA symptoms and underlines the importance of endocrine regulation of the immune response.
Highlights
Growth hormone (GH) is secreted by the anterior pituitary in vertebrates
To analyze the effect of growth hormone (GH) in immune response regulation, we tested its effect in a murine model of collagen-induced arthritis (CIA) on a mouse strain transgenic for bovine GH (bGH) under the control of the rat phosphoenolpyruvate carboxykinase promoter; these mice showed constant circulating GH (~5 μg/ml) [18]
The CIA model allows the study of the priming phase of the disease, which consists of activation of the collagen type II-specific immune response as well as the inflammatory effector phase, characterized by local inflammation, and spleen (Table 2)
Summary
Growth hormone (GH) is secreted by the anterior pituitary in vertebrates. initially defined as a major stimulant in somatic growth control, it is a pleiotropic hormone that affects many physiological functions. Several in vitro and in vivo studies demonstrate GH involvement in immune regulation, and the GH receptor is expressed by several leukocyte subpopulations [6]. T cell engraftment in severe combined immunodeficiency mice [8], improves B cell responses and antibody production [9, 10], and modulates NK cell [11] and macrophage activity [12] as well as in vivo Th1/Th2 and humoral immune responses [13]. GH administration and neutralization of TNFα reduce mucosal inflammation in experimental colitis [14]; by altering tolerization mechanisms such as the cytokine environment, macrophage polarization, activation of the suppressor T cell population, and Th17 cell plasticity, GH reduces type I diabetes development [15]
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