Title: Decreased Interleukin-2 Production from Cultured Peripheral Blood Mononuclear Cells in Human Acute Starvation<sup>1</sup>
Abstract: Depressed cell-mediated immunity and decreased insulin-like growth factor I (IGF-I) are observed in malnourished humans. To study the interaction among nutrition, IGF-I, and cytokines, healthy volunteers (six men and four women, aged 21–38 yr, weighing 93–124% of ideal body weight) were subjected to a 7-day fast (mineral water only). Fasting steadily decreased serum IGF-I from 247 ± 29 (prefast) to 87 ± 10 ng/mL (postfast; P < 0.0001), total T cells (CD3+) from 1499 ± 68 to 1308 ± 70× 109 (P < 0.0001), and T helper cells (CD4+) from 997 ± 62 to 856 ± 55 × 109 (P < 0.001). Peripheral blood mononuclear cells were isolated and cultured in serum-free RPMI 1640 for 24 h. Fasting attenuated peripheral blood mononuclear cell production of interleukin-2 in response to various concentrations of phytohemagglutinin P [PHA-P; 347 ± 48 (prefast) vs. 135 ± 52 pg/mL (postfast) when challenged with 3 μg/mL PHA-P; P < 0.005 when comparing dose-response curves (1–100 μg/mL PHA-P)]. Although the approximately 3-fold suppression of interleukin-2 and IGF-I in subjects fasted for 1 week is not likely to affect immune function significantly, our results with this short term model of nutrient restriction provide insight into possible mechanisms for immune suppression in chronic starvation.