The ability of the pleotropic, proinflammatory cytokine interleukin-6 (IL-6) to affect the replication, latency, and reactivation of herpes simplex virus type 1 (HSV-1) in cell culture and in IL-6 knockout (KO) mice was studied. In initial studies, we found no effect of exogenous IL-6, monoclonal antibodies to IL-6, or monoclonal antibody to the IL-6 coreceptor, gp130, on HSV-1 replication in vitro by plaque assay or reactivation ex vivo by explant cocultivation of latently infected murine trigeminal ganglia (TG). Compared with the wild-type (WT) mice, the IL-6 KO mice were less able to survive an ocular challenge with 105 PFU of HSV-1 (McKrae) (40% survival of WT and 7% survival KO mice; P = 0.01). There was a sixfold higher 50% lethal dose of HSV-1 in WT than IL-6 KO mice (1.7 × 104 and 2.7 × 103 PFU, respectively). No differences were observed in titers of virus recovered from the eyes, TG, or brains or in the rates of virus reactivation by explant cocultivation of TG from latently infected WT or KO mice. Exposure of latently infected mice to UV light resulted in comparable rates of reactivation and in the proportions of WT and KO animals experiencing reactivation. Moreover, quantitative PCR assays showed nearly identical numbers of HSV-1 genomes in latently infected WT and IL-6 KO mice. These studies indicate that while IL-6 plays a role in the protection of mice from lethal HSV infection, it does not substantively influence HSV replication, spread to the nervous system, establishment of latency, or reactivation.

Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, famciclovir and valacyclovir, were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1). Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same. Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences.

We used whole-mount immunocytochemistry to characterize the distribution of serotonin in the stomatogastric nervous systems of seven species of crayfish representing three genera from the family Cambaridae (Orconectes, Cambarus, and Procambarus) and one from the family Astacidae (Pacifastacus). In all species, we observed serotonin-like immunoreactivity in four gastropyloric receptor (GPR) neurons located in the lateral ventricular nerves, with one pair of neurons in each nerve. As in other crustaceans, the GPR axons project to the stomatogastric ganglion and to the bilateral commissural ganglia. In three crayfishes, we observed the GPR axons crossing the commissural ganglia, and extending toward the thoracic nervous system. This feature was most clearly and consistently seen in Pacifastacus leniusculus. The number of stained somata in the commissural ganglia varied among crayfish species from two (in Procambarus clarkii) to five (in Pacifastacus leniusculus). The largest soma (the L cell) displayed both serotonin- and tyrosine hydroxylase-like immunoreactivity in all species, suggesting that serotonin and dopamine are cotransmitters in this cell. The inferior esophageal nerve and a branch of this nerve (the inner labral nerve) contained several axons with serotonin-like immunoreactivity. These axons were clearly present in only one species (Procambarus clarkii). Serotonin acts as a neuromodulator of rhythms produced by circuits in the crab and lobster stomatogastric ganglion, and is likely to play a similar role in crayfish. Differences are apparent in the distribution of serotonin among crayfish species and between crayfish and other crustaceans, and could result in differences in the physiological action of this modulator.

Murine models of gamma interferon (IFN-␥