Background Studies have shown that stress and exercise elicit opposing immuno-modulatory effects. In concordance, we have previously demonstrated that daily, moderate exercise systemically suppresses inflammatory responses by inhibiting NFκB in an acute model of inflammation. Conversely, we have also shown that repeated social stress stimulates proinflammatory immune cell egress and trafficking, which would exacerbate autoimmunity. Chronic levels of inflammation are the hallmark of autoimmune disease and are ever-present, contributing factors leading to localized and systemic disease pathogenesis. NZM2410 mice spontaneously develop severe, early-onset glomerulonephritis at 22-40 weeks of age and are commonly used as a model for lupus nephritis.
Objectives The goal of this study was to examine the effects of both moderate exercise and social stress on chronic autoimmune-mediated inflammation in the NZM2410 model of lupus nephritis.
Methods Mice were exercised daily for 45 min by treadmill walking at moderate intensity (8 m/min) beginning at 18 weeks of age. To disturb the social order in a home cage of mice, an aggressive intruder was introduced to induce repeated social disruption stress (SDR). SDR was performed daily for 6 consecutive days beginning at 20 weeks of age. To gauge overall health, weekly blood urea nitrogen (BUN) levels were measured from serum and weights were recorded. Early removal criteria was defined by a threshold of 20% weight loss and a BUN level above 50 mg/dL. Kidney tissue was collected at experimental endpoint for H&E staining. Each time a mouse undergoing SDR met the early removal criteria, an age-matched control counterpart was selected at random for comparative analysis by histopathological scoring.
Results With daily moderate exercise, only 50% of the mice met the early removal criteria at the 39 week time point. In contrast, all control mice met this criteria by 34 weeks of age. Additionally, SDR significantly induced more severe inflammatory pathology in mice, as reflected histopathologically by glomerular hypercellularity and hyperplasia of the Bowman's capsule.
Conclusions Collectively, our data suggests that stress reduction and moderate exercise could be very potent therapeutic modalities to be used to control the chronic inflammation associated with lupus nephritis and other autoimmune diseases; thus identifying measures patients may consider that could ultimately influence disease management and even clinical outcome. Ongoing work associated with this study includes serum cytokine analysis and additional histological examination to both quantitate renal inflammation and to characterize infiltrates using immunohistochemistry.
Blazek, A, et al. Exercise Suppresses Systemic Inflammation via Inhibition of Nf-Kb Activation in Monocytes. Ann Rheum Dis 2014;73:Suppl 2 102 doi:10.1136/annrheumdis-2014-eular.3914
Powell, ND, et al., Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via beta-adrenergic induction of myelopoiesis. Proc Natl Acad Sci U S A, 2013. 110(41): p. 16574-9.
Acknowledgements Funding for this work was provided through the Wexner Medical Center at The Ohio State University.
Disclosure of Interest None declared
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