THE INFLUENCE OF VEHICLE GAVAGE ON SEASONALITY OF IMMUNE-SYSTEM PARAMETERS IN THE B6C3F1 MOUSE

Seasonal hyporesponsiveness and other immune system variations were ob served in female B6C3F1 mice during routine screening tests for immuno modulation. In a retrospective assessment, 4 years of data from over 1 200 naive, vehicle, and immunosuppressed (cyclophosphamide-treated) co ntrol mice were compiled and analyzed for uniformity and significant c ircannual pattern of immune response. Endpoints included body, spleen, and thymus weights and an immunotoxicity assessment which enumerates specific antibody plaque-forming cells (PFC) in the spleen following i mmunization with sheep red blood cells. Dosing vehicles were water, co rn oil, or 1% methyl cellulose instilled by oral gavage in a 5-20 ml/k g volume once daily for 5 days. Four days later, terminal organ and bo dy weights were recorded and PFC were quantitated. Upon analysis, indi vidual datapoints were arrayed in consistent circannual and seasonal p atterns. In naive mice, the yearly peak response in circannual rhythm (acrophase) for body weight and PFC parameters occurred in the summer, with acrophases for spleen and thymus weights located in the spring. Vehicle gavage modulated the circannual/seasonal means and acrophases of all measured endpoints in distinct patterns which varied by vehicle . Body weight was the endpoint least affected by vehicle treatment. Co rn oil was the vehicle resulting in the most dramatic effects on natur al rhythm. As expected, the naive mice receiving an ip injection of cy clophosphamide exhibited significant decreases (p less than or equal t o 0.05) in circannual mean values for PFC response and relative organ weights when compared to naive controls and the elimination of signifi cant expression of rhythm for PFC parameters. Our results indicate tha t dosing vehicles alter normal seasonal patterns of biological respons es in the mouse. These effects on natural rhythms should be considered in toxicity evaluations, especially when comparing datapoints collect ed at different times of the year. (C) 1997 Society of Toxicology.