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.
Lee
A M
AM
Department of Internal Medicine, University of Texas Medical School, Houston 77030.
Vadhan-Raj
S
S
Hamilton
R F
RF
Scheule
R K
RK
Holian
A
A
D016190:Carboplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood / Q000627:therapeutic use*; D007700:Kinetics; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D015345:Oligonucleotide Probes; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000628:therapy*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D013481:Superoxides / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007376:Interleukin-2; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015240:Phorbol 12,13-Dibutyrate; D016190:Carboplatin