Pleiotropic cytokines such as interleukin-1α (IL-1α) have multiple effects on peripheral blood monocytes (PBMs). This study examined the ability of in vivo recombinant human IL-1α (rhIL-1α) therapy to enhance clinically important monocyte functions in ovarian cancer patients prior to chemotherapy. After 4 days of continuous infusion, in vivo rhIL-1α therapy amplified both the number and activity of PBMs. Therapy with rhIL-1α increased the number of PBMs sixfold. These monocytes had a significantly increased ability to produce superoxide anion in response to phorbol 12,13- dibutyrate stimulation. Their ability to secrete spontaneously the immunomodulatory cytokines IL-1α and IL-1β was significantly increased, but their ability to secrete tumor necrosis factor α (TNF-α) was not significantly elevated. These effects of rhIL-1α infusion on cytokine secretion by PBMs appear to be related to rhIL-1α-induced increases in the mRNA levels for these cytokines. In contrast, rhIL-1α therapy did not significantly alter PBM response to lipopolysaccharide (10 μg/ml). In summary, infused rhIL-1α, in addition to its use as a myeloprotective agent, has enhancing effects on the number and activity of PBMs. The effects of rhIL-1α infusion on PBM function demonstrated here should at least transiently increase the ability of monocytes to combat infection and enhance host immune response.
- superoxide anion
- tumor necrosis factor α