Contents lists available at ScienceDirect Journal of Neuroimmunology journal homepage: www.elsevier.com/locate/jneuroim Etoricoxib inhibits peripheral inflammation and alters immune responses in intracerebroventricular colchicine injected rats Susmita Sil 1 , Tusharkanti Ghosh ⁎ Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, India ARTICLE INFO Keywords: Colchicine Etoricoxib Cox-2 Peripheral immune responses ABSTRACT The present study was designed to investigate the effectiveness of etoricoxib induced inhibition of neuroin- flammation by studying the peripheral inflammatory markers and select immune parameters in in- tracerebroventricular colchicine injected rats (ICIR). Results showed time dependent upregulation of the in- flammatory markers in the serum along with alterations of peripheral immune parameters in ICIR and dose- dependent recovery was observed upon administration of etoricoxib to ICIR; most of these effects were greater with the longer duration of study. The present study indicates that colchicine induced neuroinflammation may cause systemic inflammation and alteration of immune responses which are mediated by increased cox- 2 ac- tivity. 1. Introduction Alzheimer's disease (AD) is a progressive neurodegenerative disease (Huberman et al., 1999; Jellinger and Bancher, 1996) but the me- chanism of neurodegeneration is complicated and not yet clearly known. Different types of animal models have been used to investigate the mechanism of neurodegeneration in AD (Eijkenboom et al., 2000; Kumar et al., 2007; Rai et al., 2013; Nazem et al., 2015). Several au- thors have proposed neuroinflammation to be one of the causative factor for neurodegeneration in different chemically induced animal models of AD, e.g., streptozotocin (STZ), okadaic acid and in- tracerebroventricular (icv) colchicine injected rats (Nazem et al., 2015; Sil et al., 2015). Sil et al. (2014) reported cyclooxygenase (cox) induced neuroinflammation mediated neurodegeneration in icv colchicine in- jected rats, as naproxen (a non-specific cox blocker) could inhibit this neuroinflammation mediated degeneration. Kumar et al. (2006) also reported that colchicine induced cognitive impairments, oxidative and nitrosative stress was inhibited by cox- inhibitors. Sil and Ghosh (2016) has further shown that cox-2 expression and activity were increased in the hippocampus of intracerebroventricular colchicine injected rats (ICIR) and specific cox-2 blocker etoricoxib inhibited not only cox-2 expression and activity but also neuroinflammation, neurodegeneration and memory impairments. Thus it appears that cox-2 plays a major role in the process of colchicine induced neurodegeneration. Neuroinflammation in the brain may have influence on the per- iphery as blood brain barrier was impaired in neuroinflammation (de Vries et al., 1997). A bi - directional communication between brain and periphery has been proposed by several workers (Nicola et al., 2013). In ICIR the higher level of TNF α, reactive oxygen species (ROS) and ni- trite in brain were associated with the increased levels of these in- flammatory markers in the periphery (Sil et al., 2014). Even some of the peripheral immune responses were found to be changed in colchicine injected rats indicating the altered inflammatory status in the periphery (Sil et al., 2014). Furthermore cox-2 expression and its activity as measured by PGE 2 in hippocampus were increased in ICIR (Sil and Ghosh, 2016). It was opined that the higher level of inflammatory markers in periphery may also induce the cox activity and thereby may further influence the immune responses (Sil et al., 2014). The periph- eral inflammation and altered immune responses in ICIR are probably reflections of the central inflammation in these rats. In support of this contention it was found that administration of non-specific cox blocker not only inhibited the neuroinflammation in ICIR, but also showed concurrent regaining of the colchicine induced alteration of observed peripheral immune responses (Sil et al., 2014). Though the direct effect of cox inhibitor on periphery is a possibility but the brain source of inflammatory markers will continue to pass in periphery and may not be completely controlled by peripheral action of cox blockers. Etoricoxib has been able to reduce the colchicine induced https://doi.org/10.1016/j.jneuroim.2018.01.018 Received 20 July 2017; Received in revised form 7 January 2018; Accepted 24 January 2018 ⁎ Corresponding author at: Neurophysiology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700 009, West Bengal, India. 1 Susmita Sil is presently a Post-Doctoral Research Associate at the Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA. E-mail address: tusharkantighosh53@yahoo.in (T. Ghosh). Journal of Neuroimmunology 317 (2018) 15–23 0165-5728/ © 2018 Elsevier B.V. All rights reserved. T