Aspirin and thymosin increase interleukin-2 and interferon-gamma production by human peripheral blood lymphocytes

Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) have recently been added to the arsenal of synthetic biological response modifiers with important immunomodulatory activities. In this paper we have assessed the effects of acetylsalicylic acid (aspirin), thymosin alpha and thymosin fraction 5 (TF5), a partially purified calf thymic preparation, on production of IFN-gamma in vitro. Stimulation by oral aspirin of IL-2 and IFN-gamma production by peripheral blood lymphocytes (PBLs) was also studied in healthy human volunteers. Aspirin, thymosin alpha 1 and TF5 were all observed to enhance phytohemagglutinin (PHA)-stimulated production of IFN-gamma. Peak IFN-gamma production by PHA-stimulated PBLs was observed after 24 h of incubation with TF5 and after 72 h with aspirin. Stimulation by aspirin and TF5 required the presence of macrophages, and was additive and dose-dependent. The additive effects of aspirin and TF5 suggest that these agents act by different mechanisms. Oral administration of aspirin in normal volunteers significantly enhanced production of both IFN-gamma and IL-2. PHA-stimulated IFN-gamma production was greatest 24 h after aspirin ingestion; in contrast, IL-2 production was optimal 10 h after aspirin ingestion. These observations suggest that oral aspirin is an effective biological response modifier in humans and raise the possibility of a novel combination approach to immunomodulation involving cyclooxygenase inhibitors and thymosins.