Effects of Prolactin Deficiency on Myelopoiesis and Splenic T Lymphocyte Proliferation in Thermally Injured Mice

Abstract

The importance of prolactin (PRL) in mammopoiesis and milk production is undisputed. However, previous studies investigating the role of PRL in immune function have yielded inconsistencies. These inconsistencies have led to our hypothesis that the immunomodulatory effects of PRL are only manifest under conditions in which the organism is subjected to stress. Thermal injury is a well-known stressor. The goal of this study was to determine whether the lack of PRL enhanced the negative effects of thermal injury-induced immune alterations utilizing a mouse model in which the PRL gene had been disrupted. Mice received either sham or burn treatment, and were sacrificed 4 days later. The immune parameters studied were the capacity of bone marrow cells to form granulocyte-macrophage colony forming units (GM-CFU) in the presence of granulocyte-macrophage colony stimulating factor, and the ability of the splenic T lymphocytes to proliferate in response to phytohemagglutin (PHA). As shown by others, our results reveal that burn increased the number of GM-CFU compared to sham controls; however, this elevation was only significant in the PRL-/- mice. Thermal injury increased PHA-stimulated proliferation of splenic T lymphocytes, however this increase was only significant in the PRL+/- group. We conclude that under conditions of a controlled stress event (thermal injury) [a] the increase in the GM-CFU is exaggerated in the absence of PRL, and [b] the enhancement of PHA-induced proliferation of splenic lymphocytes required PRL. This study supports the hypothesis that the immunomodulatory effects of PRL are manifest when the organism is subjected to stress.

Protein hormones and immunity

“…Indeed, GH improves several aspects of the immune response following in vivo treatment of rats with dexamethasone or after surgical stress (Hinton et al, 1995). It was later discovered that targeted disruption of the PRL gene impairs mitogen-induced proliferation of splenocytes in thermally-injured mice but not in normal controls (Dugan et al, 2002). Findings such as these led to the clinical use of GH to improve growth in children undergoing long-term-glucocorticoid treatment, which increases catabolism caused by its effects on tissue protein synthesis and degradation, following liver transplantation (Sarna et al, 1996) and to reduce muscle loss in wasting AIDS and cancer patients (reviewed by Kelley, 2004).…”

Mechanism of Prostaglandin (PG)E2-Induced Prolactin Expression in Human T Cells: Cooperation of Two PGE2 Receptor Subtypes, E-Prostanoid (EP) 3 and EP4, Via Calcium- and Cyclic Adenosine 5′-Monophosphate-Mediated Signaling Pathways

“…Indeed, PRL administration following hemorrhagic shock in mice restored the decreased ability of macrophages to release cytokines, and thus decreased mortality from subsequent sepsis (14). Also, in PRL Ϫ/Ϫ mice, the lack of PRL enhanced the negative effects of thermal injury on myelopoiesis and T lymphocyte proliferation (15).…”

S179D prolactin diminishes the effects of UV light on epidermal gamma delta T cells

“…This demonstrates an important role for some form of PRL in stress-related immune modulation and provides a rationale for the elevation in PRL observed during stress (Almeida et al, 2000;Halford et al, 2003;Zelena et al, 2004). The particular stressor chosen for study by the Horseman laboratory was thermal injury to the skin (Dugan et al, 2002(Dugan et al, ,2004a and therefore involved both LC and γδT. A crucial role for γδT in the survivability of thermal injury to the skin has been described by Schwacha et al (2000).…”

“…In both of these models no substantive immune dysfunction was observed in non-stressed animals. Under conditions of stress, however, the PRL null mouse showed significant immunodeficiencies compared to normal mice (Dugan et al, 2002). This demonstrates an important role for some form of PRL in stress-related immune modulation and provides a rationale for the elevation in PRL observed during stress (Almeida et al, 2000;Halford et al, 2003;Zelena et al, 2004).…”