Methimazole-Induced Hypothyroidism Enhances HSV-1 Infectivity without Altering Circulating Leukocytes in the Rat

Backgrounds & In addition to their genomic actions, thyroid hormones (THs) can modulate the immune responses through cell surface receptors. One of these is the antiviral effect of THs. Methimazole, as an anti-thyroid compound, is widely used to treat hyperthyroid patients. It also reduces blood leukocytes, granulocytes in particular, and thereby may affect the immune response. Recently, we reported that methimazole-induced hypothyroidism intensifies herpes simplex virus-1(HSV-1) infectivity. To determine whether the effect is mediated through alterations in circulating leukocytes, we assessed the HSV-1 infectivity and circulating leukocytes in methimazole-induced hypothyroid rat. Male Sprague Dawley rats received methimazole (200 μg/ml) in their drinking water for 2 weeks. Rats were then inoculated with a non-lethal single dose of HSV-1, and sacrificed 3 days later to harvest their spleen. Spleen extract was prepared, and virus yield was determined by evaluation of cytopathic effects (CPE) induced by the extract in a Vero cell culture system. For quantitative analysis, standard method of Reed-Muench was employed. The routine Wright’s staining protocol was used for blood leukocytes differential count. The CPE development was significantly increased in the cell cultures exposed to the spleen extract of methimazole-treated animals (P < 0.05), indicating a higher virus yield and intensified virus infectivity. However, the effect of methimazole on blood leukocytes was minimal. Our data suggest that methimazole increases the susceptibility to HSV-1 infection, at least in part, by blocking THs synthesis but not alterations in circulating leukocytes.