Andrea A. Bohn

Examining the relationship between impaired host resistance and altered immune function in mice treated with TCDD.

Exposure to TCDD suppresses the immune response to numerous antigens, including bacterial and viral pathogens. Although we administer a non-lethal infection with influenza A virus, we often observe significant mortality in TCDD-treated animals. With the goal of identifying which TCDD-induced defects impair host resistance, we conducted a dose response study to examine whether alteration of particular immunological endpoints could be correlated with mortality. C57Bl/6 mice were treated with vehicle control, or 1, 2.5, 5, 7.5 or 10 microg/kg TCDD 1 day prior to intranasal (i.n.) infection with influenza virus. Survival was monitored for 9 days, when remaining mice were sacrificed and multiple endpoints evaluated. Lymphocyte migration to the lung and the production of virus-specific IgG2a, IgG1, and IgG2b antibodies were significantly diminished, even at the lower doses. IgA was enhanced in all groups treated with TCDD. In contrast, T cell expansion in the lymph node, and the production of IFNgamma and IL-12 were relatively resistant to suppression. Treatment with TCDD also enhanced pulmonary neutrophilia in infected mice. These results suggest that decreased antibody production and hyperinflammation may contribute to the death of TCDD-treated mice, and underscore the importance of evaluating numerous endpoints before concluding that a chemical is or is not immunotoxic.

What is your diagnosis? Intracranial mass in a dog

A 6-year-old male neutered Rhodesian Ridgeback dog was presented for a 6-week history of uncharacteristic aggressive behavior, left-sided circling, pacing, and seizure activity. The owner also reported that the dog had become inappetent and lethargic, was straining to urinate and defecate, and had shifting-leg lameness. Upon presentation, the dog was lethargic but responsive and in good body condition. A neurologic examination was performed and abnormalities in gait, postural reactions, spinal reflexes, and pain perception were not detected. Results of a CBC, biochemical profile, and urinalysis were unremarkable, and abnormalities were not found on thoracic radiographic and abdominal ultrasonographic examinations. Magnetic resonance imaging (MRI) revealed a mass that was 5.0 9 2.8 9 2.7 cm and extended from the right olfactory lobe with involvement of the right and left frontal lobes, hypothalamus, and portions of the basal nuclei. Mixed-signal intensity with distinct hypoand hyper-intense regions was noted within the mass and suggested a cystic component with areas of hemorrhage and mineralization. Owing to the extensive nature of the mass, surgical excision was not attempted and the patient was euthanized and submitted for necropsy examination. Fine-needle aspirates and impression smears of an excised portion of the mass were collected at necropsy for cytopathologic examination (Figure 1). Figure 1. Imprint of a cerebral mass obtained at necropsy. WrightGiemsa,9100 objective.