Increase in transforming growth factor-beta in the brain during infection is related to fever, not depression of spontaneous motor activity.

When viral infection occurs, this information is transmitted to the brain, and symptoms such as fever and tiredness are induced. One of the causes of these symptoms is the secretion of proinflammatory cytokines in blood and the brain. In this study, the i.p. administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA, to rats was used as an infection model. Poly I:C decreased spontaneous motor activity (SMA) 2 h after i.p. administration, and this decrease was maintained thereafter. The concentration of active transforming growth factor-beta (TGF-beta) in cerebrospinal fluid (CSF) increased 1 h after the administration. This increase occurred earlier than those in the concentrations of other proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in serum. The intracisternal administration of an anti-TGF-beta antibody partially inhibited fever induced by poly I:C administration; however, this treatment did not affect the decrease in SMA. Furthermore, intracisternal administration of TGF-beta raised the body temperature. These results indicate that TGF-beta in the brain, which was increased by poly I:C administration, is associated with fever but not with a decrease in SMA.