Repeated Stress Down-Regulates β2- and α2C-Adrenergic Receptors and Up-Regulates Gene Expression of IL-6 in the Rat Spleen

Catecholamines are among first compounds released during stress, and they regulate many functions of the organism, including immune system, via adrenergic receptors (ARs). Spleen, as an immune organ with high number of macrophages, possesses various ARs, from which beta(2)-ARs are considered to be the most important for the modulation of immune functions. Nevertheless, little is known about the regulation and involvement of ARs in the splenic function by stress. Therefore, the aim of this work was to measure the gene expression of ARs and several cytokines in the spleen of rats exposed to a single and repeated (14x) immobilization stress (IMO). We have found a significant increase in beta(2)-AR mRNA after a single IMO, but a significant decrease in beta(2)-AR mRNA and protein level after repeated (14x) IMO. The most prominent decrease was detected in the gene expression of the alpha(2A)- and alpha(2C)-AR after repeated IMO. However, changes in mRNA were translated into protein levels only for the alpha(2C)-subtype. Other types of ARs remained unchanged during the stress situation. Since we proposed that these ARs might affect production of cytokines, we measured gene expression of pro-inflammatory (TNF-alpha, IL-1 beta, IL-6 and IL-18) and anti-inflammatory (IL-10 and TGF-beta 1) cytokines. We detected changes only in IL-6 and IL-10 mRNA levels. While IL-6 mRNA was increased, IL-10 mRNA dropped after repeated IMO. According to these results we suggest that changes of beta(2)- and alpha(2C)-ARs participate in IL-6-mediated processes in the spleen, especially during chronic stress situations.