Radiation causes increased production and decreased utilization of IL-2 in human mononuclear cells.
The effects of radiation on the kinetics of Interleukin-2 (IL-2) production and utilization by mononuclear cells (MNCs) were studied. Mononuclear cells from normal, healthy individuals were subjected to various doses of radiation ranging from 0 to 2,000 rad and cultured in the presence of PHA. Supernatants from these cultures were harvested at various periods and their IL-2 contents determined by both the standard bioassay and ELISA. A radiation dose of 800 rad and higher had a marked effect on both IL-2 production and consumption. Although the supernatants from both the irradiated and non-irradiated MNCs contained maximal concentrations of IL-2 between 8 and 24 h of culture, the former had three times as much IL-2 as the latter. An increase in IL-2-mRNA levels was also noticed in irradiated, PHA-stimulated cells. Moreover, the supernatants from irradiated MNCs collected as late as 72 h after the initiation of culture contained more than 30% of the total IL-2 produced compared to less than 8% in supernatants from non-irradiated cells. Supernatants from non-irradiated cells incubated further with irradiated cells contained relatively higher quantities of IL-2 than those incubated continuously with non-irradiated cells. Supernatants from co-cultures of irradiated and non-irradiated MNCs contained less than expected amounts of IL-2 in two of the three subjects. Despite a difference in both the production and consumption of IL-2 between the irradiated and non-irradiated cells, there was no difference in their ability to generate IL-2 receptors. The results indicate that inactivation of radiosensitive suppressor T cells is associated with superinduction of IL-2 mRNA, increased production and decreased consumption of IL-2 by MNCs, thereby resulting in increased accumulation of IL-2.
Venkataraman
M
M
Department of Medicine, Mount Sinai Hospital Medical Center, Chicago, IL.
Westerman
M P
MP
D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000528:radiation effects
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2