Seasonal influence on mitogen and cyclosporin responses of peripheral blood lymphocytes

The immune response and lymphocyte activation in particular are affected by environmental factors. In vivo and in vitro experiments demonstrate variability in lymphocyte activation according to seasonal changes. This study focused on the effects of season on the ex vivo mitogen-induced activation of lymphocytes from peripheral blood of healthy humans living in a temperate climate, as well as the ex vivo lymphocyte activation of rabbits living under constant laboratory conditions. The possible impact of season on the action of the immunosuppressant drug cyclosporin A (CsA) on lymphocyte activation was investigated in both species. Cultured peripheral blood lymphocytes from human donors (n=13, 22-63years of age) and from animals housed under 12:12hour light:dark cycle were stimulated with phytohemagglutinin (PHA) in the absence or presence of 10 and 25μg/mL CsA. Lymphocyte activation was assessed by morphometric analysis under a light microscope. Percentages of unactivated lymphocytes, activated lymphoblasts and aberrant cells reflecting cytotoxicity were determined. Human lymphocytes demonstrated a significant decrease in response to PHA during the winter months, in comparison to the rest of the year. In contrast, the peripheral blood lymphocytes of rabbits housed under constant conditions did not demonstrate similar variations in response to PHA stimulation. The immunosuppressive action of cyclosporin A on this experimental model was unaffected by the observed seasonal variation in mitogen response in humans. These findings may guide research towards the identification of factors associated with the seasonality of the immune response and its potential influence on therapeutic interventions.