Abstract
Spleen is an immune organ innervated with sympathetic nerves which together with adrenomedullary system control splenic immune functions. However, the mechanism by which prior stress exposure modulates the immune response induced by immunogenic challenge is not sufficiently clarified. Thus, the aim of this study was to investigate the effect of a single (2 h) and repeated (2 h daily for 7 days) immobilization stress (IMO) on the innate immune response in the spleen induced by lipopolysaccharide (LPS, 100 µg/kg). LPS elevated splenic levels of norepinephrine and epinephrine, while prior IMO prevented this response. LPS did not alter de novo production of catecholamines, however, prior IMO attenuated phenylethanolamine N-methyltransferase gene expression. Particularly repeated IMO exacerbated LPS-induced down-regulation of α1B- and β1-adrenergic receptors (ARs), while enhanced α2A- and β2-AR mRNAs. Elevated expression of inflammatory mediators (iNOS2, IL-1β, IL-6, TNF-α, IL-10) was observed following LPS and repeated IMO again potentiated this effect. These changes were associated with enhanced Ly6C gene expression, a monocyte marker, and elevated MCP-1, GM-CSF, and CXCL1 mRNAs suggesting an increased recruitment of monocytes and neutrophils into the spleen. Additionally, we observed increased Bax/Bcl-1 mRNA ratio together with reduced B cell numbers in rats exposed to repeated IMO and treated with LPS but not in acutely stressed rats. Altogether, these data indicate that repeated stress via changes in CA levels and specific α- and β-AR subtypes exaggerates the inflammatory response likely by recruiting peripheral monocytes and neutrophils to the spleen, resulting in the induction of apoptosis within this tissue, particularly in B cells. These changes may alter the splenic immune functions with potentially pathological consequences.
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The authors would like to acknowledge the financial support provided through a grant from Slovak Research and Development Agency (No. APVV-0088-10) and VEGA Grants 2/0067/14 and 2/0036/11.
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ML and PV contributed equally to this work. ML was involved in creating the experimental design, performing tissue dissection and processing for RNA isolation and Real-Time PCR analysis, statistical evaluation of the data, and writing the manuscript. PV performed all procedures with the experimental animals, designed the primers, and performed additional Real-Time PCRs and was also involved in writing the manuscript. IR and GM contributed by analyzing the tissue catecholamines and statistics and prepared the final graphs. RK was involved in the whole study design and performed decapitation of the animals.
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Laukova, M., Vargovic, P., Rokytova, I. et al. Repeated Stress Exaggerates Lipopolysaccharide-Induced Inflammatory Response in the Rat Spleen. Cell Mol Neurobiol 38, 195–208 (2018). https://doi.org/10.1007/s10571-017-0546-5
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DOI: https://doi.org/10.1007/s10571-017-0546-5