In vivo administration of recombinant human interleukin-3 elicits an acute phase response involving endogenous synthesis of interleukin-6.
Interleukin-6 has been shown to stimulate in vitro synthesis of C-reactive protein (CCRP) in hepatocytes by enhancing the transcriptional rate of the CRP gene. It has also been demonstrated that IL-6 spurs the terminal differentiation of B-cells into immunoglobulin secreting cells when synergizing with IL-3. IL-6 may therefore act as a prime molecule in the acute phase and immune response. We have administered rh IL-3 to cancer patients in a phase I/II clinical trial. Endogenous IL-6 levels increased in a dose-dependent fashion upon i.v. bolus injection of rh IL-3 and continued to be significantly elevated above pretreatment levels when IL-3 was further administered by the s.c. route. Increases of IL-6 levels were associated with enhanced production of CRP in vivo detected after 24 h of injection. At day 14 of rh IL-3 treatment plasma immunoglobulin concentrations were measured and IgM was found to be increased by greater than 2.5 fold above starting levels. These results indicate that rh IL-3 also augments the acute phase response in vivo and contributes to increased synthesis of IgM and that induction of endogenous IL-6 is involved in these events.
Lindemann
A
A
Department of Hematology and Oncology, University of Freiburg, F.R.G.
Ganser
A
A
Hoelzer
D
D
Mertelsmann
R
R
Herrmann
F
F
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D002097:C-Reactive Protein / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007377:Interleukin-3 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis*; D009369:Neoplasms / Q000097:blood / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013268:Stimulation, Chemical; D014158:Transcription, Genetic / Q000187:drug effects
D000209:Acute-Phase Proteins; D007155:Immunologic Factors; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D002097:C-Reactive Protein