THE IN-VIVO EFFECTS OF RHIL-1-ALPHA THERAPY ON HUMAN MONOCYTE ACTIVITY

Pleiotropic cytokines such as interleukin-1alpha (IL-1alpha) have mult iple effects on peripheral blood monocytes (PBMs). This study examined the ability of in vivo recombinant human IL-1alpha (rhIL-1alpha) ther apy to enhance clinically important monocyte functions in ovarian canc er patients prior to chemotherapy. After 4 days of continuous infusion , in vivo rhIL-1alpha therapy amplified both the number and activity o f PBMs. Therapy with rhIL-1alpha increased the number of PBMs sixfold. These monocytes had a significantly increased ability to produce supe roxide anion in response to phorbol 12,13-dibutyrate stimulation. Thei r ability to secrete spontaneously the immunomodulatory cytokines IL-1 alpha and IL-1beta was significantly increased, but their ability to s ecrete tumor necrosis factor alpha (TNF-alpha) was not significantly e levated. These effects of rhIL-1alpha infusion on cytokine secretion b y PBMs appear to be related to rhIL-1alpha-induced increases in the mR NA levels for these cytokines. In contrast, rhIL-1alpha therapy did no t significantly alter PBM response to lipopolysaccharide (10 mug/ml). In summary, infused rhIL-1alpha, in addition to its use as a myeloprot ective agent, has enhancing effects on the number and activity of PBMs . The effects of rhIL-1alpha infusion on PBM function demonstrated her e should at least transiently increase the ability of monocytes to com bat infection and enhance host immune response.