Our results also suggest that investigating neuropsychiatric adverse effects that may develop or persist years after the therapy termination is as important as detecting these adverse effects during the antiviral therapy. Finally, prospective pharmacogenetic
studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-α-induced depression; and the search for other candidate genes that may fill the gaps in prediction of this substance-induced affective disorder must continue. The authors do not have any actual or potential conflict of interest, including any financial, personal, or other relationships with other people or organizations, selleck within three years of beginning the work submitted that could inappropriately influence, or be perceived to influence, their work. Amanda Galvão-de Almeida is supported by the National Council of Technological and Scientific Development (CNPq): 471592/2008-0; 142262/2008-0. Ângela Miranda-Scippa is recipient of the CNPq fellowship. We thank Dr. Susana Carolina Batista-Neves, Dr. selleck compound Luiz Guilherme Lyra, Dr. Nelma Pereira de Santana, Dr. Mateus Fiúza, Dr. Nádia Caldas, Dr. Maria Isabel Schinoni, Dr. Helma Cotrim, Dr. Marcelo Portugal de Souza, Dr. Antônio Ricardo Andrade, Dr. Ana Cristina
Siqueira Landim, Dr. Lourianne Nascimento Cavalcante, Dr. Aloma Conceição Campeche, Dr. Edison Parise, Dr. Delvone Almeida, Dr. Ana Thereza Gomes, and the 2008–2010 Gastroenterology residents for clinical and
technical assistance. “
“Humans and animals are constantly exposed to the risk of infection by bacterial and viral pathogens, and sub-clinical, low grade infections are reported to account for up to 35% of all general practitioner consultations in the UK (Fleming et al., 2002). These infections can initiate a set of immune, physiological, metabolic, and behavioural responses, characterised by fever, reduced activity, reduced appetite, impaired cognitive function, anxiety and depression (Hart, 1988), also known as sickness behaviour. These behavioural changes are believed to be largely triggered Terminal deoxynucleotidyl transferase by pro-inflammatory mediators that are produced by activated immune cells (Konsman et al., 2002) or by COX-2 mediated prostaglandin (PG) production in endothelial cells (Yamagata et al., 2001). More specifically, it is believed that the pro-inflammatory cytokines IL-1β (Bluthe et al., 2000a), IL-6 (Bluthe et al., 2000b and Cartmell et al., 2000) and TNF-α (Bluthe et al., 2000a) have a pivotal role in the onset of LPS-induced behavioural symptoms. These cytokines communicate with the brain by different mechanisms (Ek et al., 1998 and Konsman et al., 2000), each resulting in de novo expression of cytokines within CNS tissues and widespread activation of resident immune-competent cells within the brain, the microglia.