INHIBITION OF HUMAN LYMPHOCYTE FUNCTION BY ORGANIC-SOLVENTS

We studied the direct effect of reactive hydroxyl precursors and inhib itors on CD4+ T-cell function. We used hydrogen peroxide plus ferrous chloride as the hydroxyl radical-generating system and di-methyl sulph ourea, di-methyl sulfoxide, pyrrolidine dithiocarbonate, methanol, and ethanol, at a noncytotoxic concentration, as inhibitors. The immune p arameter studies were proliferation and interleukin-2 production by pe ripheral blood lymphocytes stimulated with anti-CD3 antibody, phytohem agglutinin and alloantigens; proliferation, interleukin-2 production a nd mRNA expression of interleukin-4 and interferon gamma by allogeneic CD4+ T-cell clones stimulated with alloantigens. The results show tha t lymphocytes produce significant amounts of reactive oxygen species a s measured by malondialdehyde produced in cultures. The hydroxyl radic al-generating system did not change any of the cellular responses stud ied although it doubled Malondialdehyde production. Hydroxyl radical s cavengers significantly inhibited all responses at doses that didn't s ignificantly decrease malondialdehyde production. DNA analysis failed to show evidence for apoptosis. Conclusion: Hydroxyl radical scavenger s inhibit lymphocyte mitogenesis by a process that is independent of s cavenging hydroxyl radicals.