**Author details**

70 Prolactin

The timing regulation of the immunological function is also influenced by the numerous changes that occur during the sleep period. Sleep promotes a striking increase in the number of myeloid dendritic cell precursors producing IL-12, which implies an induction of the Th1 responses. In addition, sleep reduces plasmacytoid dendritic cells and T-cell counts without affecting the production of IFN. Sleep also substantially decreases the number of certain subpopulations of monocytes (CD14 and CD16+), probably reflecting margination of these cells upon a sleep-related drop in catecholamine release [163]. The number of undifferentiated naïve T cells and the production of pro-inflammatory cytokines exhibit peaks during the first hours of sleep, whereas the number of circulating immune cells with immediate effector functions and the anti-inflammatory cytokine activity peak during wakefulness. Sleep also facilitates the extravasation of T-cells and their redistribution to lymph nodes. In general, sleep enhances cytokines (such as IL-12) that promote the

It has been postulated that NREM sleep facilitates the transfer of antigenic information from antigen-presenting cells to antigen-specific Th cells; as a consequence, sleep after vaccination has been observed to boost immunological memory [165]. The daily profile of circulating PRL, with elevated levels during the rest periods in mammals, raises the possibility that PRL could be one of the factors involved in the enhanced immunological response associated with sleep. This role could be related in particular to the stage of NREM sleep and its accompanying pro-inflammatory endocrine milieu with the high levels of growth hormone and PRL and low concentrations of glucocorticoids and catecholamine that occur during sleep [165]. This same idea provides a rationale for the chronobiological treatment of RA. In this protocol, a low-dose, chronotherapeutic application of prednisone at night (~03:00 h) has been suggested to improve the benefits and reduce the adverse side-effects of glucocorticoid treatment in patients with RA. The low dose of prednisone during the night is as effective as a higher dose applied during the day. Again, this pharmacological scheme could be favorable because of the conjunction between PRL and other immunological

The multiple actions of PRL and its diverse sites of synthesis evidence the versatility of this hormone/cytokine in the homeostasis of the organism. Besides the well-known actions of PRL on reproduction, it exerts multiple actions unrelated to the reproductive area. In the immune system PRL functions as a survival factor inasmuch as it promotes proliferation and inhibits apoptosis. This important role could help to maintain the appropriate number of immune cells in physiological conditions, and to maintain immune tolerance. Abnormal synthesis and secretion of PRL could lead to the breakdown of balance in the immune system, and consequently, could promote autorreactivity and bursting or aggravation of the clinical condition in autoimmune diseases. A deregulation in the mechanisms that control PRL synthesis could lead to enhanced PRL secretion. Nowadays, available information is limited on the biological significance of posttranslational modifications of the PRL in vivo, such as glycosylation or cleavage, which may exert different biological functions related to

interaction between antigen-presenting cells and T-helper cells [164].

supportive peptides and the proven clinical drugs [166].

**6. Conclusion** 

Lorenza Díaz, Leticia González, Saúl Lira-Albarrán and Fernando Larrea *Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. México, D. F. México* 

Mauricio Díaz-Muñoz and Isabel Méndez\*

*Department of Cellular and Molecular Neurobiology, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México* 
