      Document 0226
 DOCN  DRG0226
 UNIQUE IDENTIFIER        DRG-0021
 NAME OF SUBSTANCE        Aldesleukin [USAN 1995]
 REGISTRY NUMBER          110942-02-4
 RELATED REGISTRY NUMBER  94218-75-4 (Teceleukin)
 STANDARD CHEMICAL NAME   2-133-Interleukin 2 (human reduced),
                          125-L-serine- [USAN 1996]
 SYNONYMS                 IL-2 [CHEMLINE]
 SYNONYMS                 Recombinant IL-2 [NIAID ACTG 024]
 SYNONYMS                 rIL-2 [USPD DI 1995]
 SYNONYMS                 Lymphocyte Mitogenic Factor [Merck Index
                          1989]
 SYNONYMS                 T-Cell Growth Factor [Merck Index 1989]
 SYNONYMS                 TCGF [Merck Index 1989]
 SYNONYMS                 Proleukin [USAN 1995]
 SYNONYMS                 Thymocyte stimulating factor [Merck Index
                          1989]
 SYNONYMS                 Costimulator [Merck Index 1989]
 SYNONYMS                 Des-alanyl-l, serine-125 human interleukin-2
                          [PDR 1995]
 SYNONYMS                 Interleukin-2 [AMFAR Tx Dir 1993;6(3)]
 PROTOCOL ID NUMBERS      NIAID ACTG 024
 PROTOCOL ID NUMBERS      NIAID ACTG 042
 PROTOCOL ID NUMBERS      NIAID ACTG 067
 PROTOCOL ID NUMBERS      NIAID ACTG 080
 PROTOCOL ID NUMBERS      NIAID 88 I-74
 PROTOCOL ID NUMBERS      NIAID 88 I-170
 PROTOCOL ID NUMBERS      NIAID 93 CC-113
 PROTOCOL ID NUMBERS      FDA 085A
 PROTOCOL ID NUMBERS      NIAID 91 CC-143
 PROTOCOL ID NUMBERS      FDA 086A
 PROTOCOL ID NUMBERS      NIAID 93 I-205
 PROTOCOL ID NUMBERS      NIAID 94 I-76
 PROTOCOL ID NUMBERS      NIAID 95 CC-114
 PROTOCOL ID NUMBERS      NIAID IL-2 SC.
 PROTOCOL ID NUMBERS      NIAID IL-2/TNF ANTAG.
 PROTOCOL ID NUMBERS      NIAID ACTG 248
 PROTOCOL ID NUMBERS      NCI 95 C-183
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Interleukin-2, while not
                          directly antiviral, enhances cell-mediated
                          and humoral immune responses to virus and
                          viral antigen and confers resistance to
                          animal models from lethal challenge with
                          herpes viruses and bacteria, decreasing the
                          frequency of clinical recurrences. The
                          mechanism behind this suppression of chronic
                          infection appears to involve increased gamma
                          interferon and killer cell function.
                          Interleukin-2 is bound to activated cells via
                          specific receptors (one of which is known as
                          the TAC receptor), thus initiating T-cell
                          mitogenesis. In vitro exposure to optimal
                          concentrations of interleukin-2 for as short
                          as 1 hour results in thymidine incorporation
                          at 24 hours that is equivalent to that
                          observed after continuous exposure to
                          interleukin-2. This drug causes alterations
                          in the cell membrane and an increase in the
                          expression of both the TAC receptor and
                          interferon-gamma. Interferon-gamma is capable
                          of inhibiting virus replication by
                          interruption of viral RNA translation and by
                          increasing cell-mediated cytotoxicity. Human
                          and animal studies indicate biphasic serum
                          clearance kinetics. The first phase begins
                          with an initial rapid decline of 10-20 fold
                          having a half-life of 3 min (representing
                          distribution from peripheral blood into
                          interstitial fluid). The first phase is
                          followed by a slower steady-state phase (body
                          elimination) having an approximate 50-minute
                          half-life. This is consistent with the
                          standard 2-compartment model expected for a
                          16Kd protein. Lymphocytes from patients with
                          AIDS produce significantly less IL-2 than
                          cells from healthy controls and have a
                          greatly decreased proliferative response to
                          mitogen induction. Addition of IL-2 to
                          lymphocyte cultures from AIDS patients
                          partially or fully restored this response in
                          approximately 50% of treated cultures. The
                          FDA has designated interleukin-2 as an orphan
                          product (group C status) for treatment of
                          metastatic renal cell carcinoma. [NIAID ACTG
                          024] [Drug Evaluations Annual 1992]
 DISEASES STUDIED/TREATED Enhancement of immune response in HIV
                          infection [NIAID ACTG 024]
 CLASSIFICATION CODE      Immunomodulator [USAN 1995]
 CLASSIFICATION CODE      Antineoplastic [Merck Index 1989]
 OTHER MAJOR USES         Renal cell carcinoma [USP DI 1995]
 SUBSTANCE INTERACTIONS   May interact with psychotropic, nephrotoxic,
                          and chemotherapeutic agents. Glucocorticoids
                          may reduce the antitumor effects of
                          interleukin-2. [PDR 1995]
 ADVERSE EFFECTS          Adverse reactions include fever, chills,
                          rigors, neuropsychiatric disorders, fatigue,
                          anemia, eosinophilia, liver function
                          abnormalities, nephrotoxicity, emesis,
                          diarrhea, edema, weight gain. Examples of
                          adverse reactions with permanent sequelae
                          include myocardial infarctions, bowel
                          perforations or infarctions, and gangrene.
                          Most of the adverse effects resolve quickly
                          after therapy is stopped, but
                          treatment-related deaths have been reported.
                          [PDR 1995]
 CONTRAINDICATIONS        Should not be used by patients with
                          hypertension, significant cardiac disease or
                          central nervous system (CNS) lesions, nor by
                          pregnant or lactating women or patients with
                          organ allografts. [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A nonglycosylated
                          lymphokine produced by recombinant DNA
                          technology. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 15,600 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white
                          lyophillized powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORM: C690H1115N177O203S8 [USAN
                          1995]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: Corresponds to the
                          amino acid structure of purified natural
                          IL-2, except the molecule has no N-terminus
                          alanine and has serine substituted for
                          cysteine at aa position 125 [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Stable at pH 3-10 at 56 C for 60
                          min. Unstable after 30 min at 70 C [Merck
                          Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Lyophilized powder, 22 million
                          IU, for reconstitution. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous infusion. [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Reconstituted and
                          diluted solutions should be stored in a
                          refrigerator at 2C to 8C and used within 48
                          hours. [PDR 1995]
 MANUFACTURERS            Cetus
 MANUFACTURERS            Hoffmann-La Roche
 REFERENCES               Kinter AL, Bende SM, Hardy EC, Jackson R,
                          Fauci AS. Interleukin 2 induces CD8+ T
                          cell-mediated suppression of human
                          immunodeficiency virus replication in CD4+ T
                          cells and this effect overrides its ability
                          to stimulate virus expression. Proc Natl Acad
                          Sci USA. 1995 Nov 21;92(24):10985-9.
 REFERENCES               Alex S, Gupta SL, Minor JR,
                          Turcovski-Corrales S, Gallelli JF, Taub D,
                          Piscitelli SC. Compatibility and activity of
                          aldesleukin (recombinant interleukin-2) in
                          presence of selected drugs during simulated
                          Y-site administration: evaluation of three
                          methods. Am J Health Syst Pharm 1995 Nov
                          1;52(21):2423-6.
 REFERENCES               Horn CA, Washburn RG. Anticryptococcal
                          activity of NK cell-enriched peripheral blood
                          lymphocytes from human immunodeficiency
                          virus-infected subjects: responses to
                          interleukin-2, interferon-gamma, and
                          interleukin-12. J Infect Dis. 1995
                          Oct;172(4):1023-7.
 REFERENCES               Eylar EH, Baez I, Vazquez A, Colon-Martinez
                          SL, Yamamura Y. Suppressed proliferative
                          response and interleukin-2 production in
                          hispanic HIV+ and AIDS T-cell subsets. Cell
                          Mol Biol (Noisy-le-grand). 1995;41 Suppl
                          1:S25-33.
 REFERENCES               Spain BA, Soliman DM, Sidner RA, Twigg HL.
                          Enhanced proliferation and IL-2 secretion by
                          lung lymphocytes from HIV-infected subjects.
                          Am J Physiol. 1995 Oct;269(4 Pt 1):L498-506.
 REFERENCES               Brenner BG, Gornitsky M, Wainberg MA.
                          Interleukin-2-inducible natural immune
                          (lymphokine-activated killer cell) responses
                          as a functional correlate of progression to
                          AIDS. Clin Diagn Lab Immunol. 1994
                          Sep;1(5):538-44.
 REFERENCES               Klimas N, Patarca R, Walling J, Garcia R,
                          Mayer V, Moody D, Okarma T, Fletcher MA.
                          Clinical and immunological changes in AIDS
                          patients following adoptive therapy with
                          activated autologous CD8 T cells and
                          interleukin-2 infusion. AIDS. 1994
                          Aug;8(8):1073-81.
 REFERENCES               Powell FC, Spooner KM, Shawker TH, Premkumar
                          A, Thakore KN, Vogel SE, Kovacs JA, Masur H,
                          Feuerstein IM. Symptomatic
                          interleukin-2-induced cholecystopathy
                          patients with HIV infection. AJR Am J
                          Roentgenol. 1994 Jul;163(1):117-21.
 REFERENCES               Bernstein ZP, Porter M, Grimes P, Caligiuri
                          MA. Phase I study of daily subcutaneous (sc)
                          low dose interleukin-2 (IL-2) in
                          HIV-associated malignancies (Meeting
                          abstract). Proc Annu Meet Am Soc Clin Oncol.
                          1994;13:A19.
 REFERENCES               Timerman A, Hutzler RU. IL-2 administration
                          to HIV+ individuals and AIDS patients. Int
                          Conf AIDS. 1994 Aug 7-12;10(1):216 (abstract
                          no. PB0292).
 ENTRY MONTH              8906
 LAST REVISION DATE       960514
 

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