The in vivo effects of rhIL-1 alpha therapy on human monocyte activity.

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