      Document 0125
 DOCN  DRG0125
 UNIQUE IDENTIFIER        DRG-0122
 NAME OF SUBSTANCE        Interleukin-3 (human, recombinant, E. coli)
                          [AmFAR Tx Dir 1995;7(4)]
 SYNONYMS                 RhIL-3 [FDA 080A]
 SYNONYMS                 IL-3 [AmFAR Tx Dir 1995;7(4)]
 SYNONYMS                 Interleukin-3 human (recombinant) [USP DI
                          1995]
 PROTOCOL ID NUMBERS      FDA 080A
 SECONDARY SOURCE ID      SDZ ILE-964 [FDA 080A]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: IL-3 and
                          granulocyte-macrophage colony stimulating
                          factor (GM-CSF) share common binding
                          capacities on hemopoietic cells.  Both
                          molecules compete for bonding with an equally
                          high affinity to a dual GM-CSF/IL-3 receptor
                          type that was found to be present on acute
                          myeloblastic leukemia (AML) cells and normal
                          monocytes and may explain overlapping
                          biologic effects.  There is evidence for
                          IL-3-induced phosphorylation of several
                          cellular proteins including the putative
                          IL-3R subunits.  IL-3 is also a specific
                          inductor of enzymes involved in DNA/RNA
                          turnover, cell metabolism, and
                          differentiation, in particular
                          20-alpha-steroid-dehydrogenase and histidine-
                          and ornithine-decarboxylase.  Recent data
                          have shown that IL-3 directly counteracts a
                          number of mechanisms including growth
                          inhibition and cell death; thus, a number of
                          different effects of IL-3 on cell function
                          and metabolism result in induction of growth,
                          survival, and differentiation of the target
                          cells.  In hemopoiesis, IL-3 exerts
                          functional and proliferative effects on
                          multiple cell lineages.  Within the
                          hemopoietic ontogeny, IL-3 acts on
                          proliferation of early multipotential
                          progenitor cells such as CFU-GEMM, and on
                          more committed progenitor cells including
                          CFU-GM, BFU-E, and CFU-MK.  Human trials
                          indicated a rapid clearance of IL-3. The
                          half-life ranged from 13.4 to 53 minutes.
                          This short half-life suggests that IL-3
                          should be given by prolonged IV infusion;
                          alternatively, SC or IM administration may be
                          useful, as administration by these routes
                          results in prolonged serum levels. [Cancer
                          1991 May 15; 67(10) Supplement] [Drug
                          Evaluations Annual 1995] [American Journal of
                          Clinical Oncology February 1991]
 DISEASES STUDIED/TREATED Subcutaneous treatment of HIV associated
                          cytopenia [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Immunomodulator [AmFAR Tx Dir 1993;6(4)]
 CLASSIFICATION CODE      Hematopoietic [USP DI 1995]
 OTHER MAJOR USES         Promotion of erythropoiesis in
                          Diamond-Blackfan anemia (congenital pure cell
                          aplasia); for sequential administration with
                          sargramostim to accelerate neutrophil and
                          platelet recovery in autologous bone marrow
                          transplantation in Hodgkin's and
                          non-Hodgkin's lymphoma [USP DI 1995]
 SUBSTANCE INTERACTIONS   Interacts with systemic chemotherapy,
                          medications with known myelosuppressive
                          effects such as ganciclovir, trimethoprim /
                          sulfamethoxazole, dapsone, or AZT. Exhibits
                          synergistic activity with other hematopoietic
                          growth factors such as EPO, GM-CSF and G-CSF.
                          [AmFAR Tx Dir 1993;6(4)] [FDA 080A] [Drug
                          Evaluations Annual 1995]
 ADVERSE EFFECTS          Side effects can include fever, headache,
                          flushing, and local erythema at the site of
                          injection. [AmFAR Tx Dir 1995;7(4)] [Drug
                          Evaluations Annual 1995]
 CONTRAINDICATIONS        Contraindicated in the presence of hepatic or
                          renal dysfunction, documented allergic
                          disorder such as asthma, history of
                          anaphylaxis, atopy, serum sickness, or
                          bronchospasm. [FDA 080A]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: IL-3 is one of several
                          colony-stimulating factors which regulate the
                          proliferation and differentation of
                          hematopoietic and lymphoid cells. IL-3 is the
                          recombinantly produced protein [AmFAR Tx Dir
                          1995;7(4)]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Recombinant IL-3
                          produced by bacteria is not glycosylated but
                          still exhibits biological activities similar
                          to those of naturally produced IL-3 [Amer J
                          Clin Oncology February 1991]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 24,000 daltons [Drug
                          Evaluations Annual 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous injection.
                          [AmFAR Tx Dir 1995;7(4)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Injection. [Drug Evaluations
                          Annual 1995]
 MANUFACTURERS            Sandoz Pharmaceuticals
 REFERENCES               Von Roenn JH, Gordon LI, Grace W, Anderson J,
                          Eickhoff C. Phase I trial of rIL-3 plus
                          zidovudine (ZDV) in HIV positive patients
                          with neutropenia (meeting abstract). Proc
                          Annu Meet Am Soc Clin Oncol. 1994;13:A17.
 REFERENCES               Scadden DT, Wang A, Zsebo KM, Groopman JE. In
                          vitro effects of stem-cell factor or
                          interleukin-3 on myelosuppression associated
                          with AIDS. AIDS. 1994 Feb;8(2):193-6.
 REFERENCES               Weinberg RS, Chusid ED, Galperin Y, Cheung T,
                          Sacks H. Stem cell factor and IL-3 stimulate
                          vitro growth of erythroid progenitor cells
                          from HIV+ patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):171 (abstract no. PO-A13-0219).
 REFERENCES               Fiorelli G, Carandini D, Gaviraghi A, Velati
                          C, Lazzarin A, Galli M, Cappellini MD. IL-3,
                          and stem cell factor, significantly reduces
                          the inhibitory effect of zidovudine on in
                          vitro erythroid progenitors growth. Int Conf
                          AIDS. 1992 Jul 19-24;8(2):B213 (abstract no.
                          PoB 3732).
 REFERENCES               Tolomeo M, Mancuso S, Luparello M, Perricone
                          R, Abbadessa V, Cajozzo A. Effects of
                          cytokines and interferons on myelopoietic
                          activity in granulocytopenic HIV+ patients.
                          Int Conf AIDS. 1991 Jun 16-21;7(2):160
                          (abstarct no. W.A.1273).
 REFERENCES               Schuitemaker H, Kootstra NA, van Oers MH, van
                          Lambalgen R, Tersmette M, Miedema F.
                          Induction of monocyte proliferation and HIV
                          expression by IL-3 does not interfere with
                          anti-viral activity of zidovudine. Blood.
                          1990 Oct 15;76(8):1490-3.
 ENTRY MONTH              9108
 LAST REVISION DATE       951213
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
