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Expert Opinion on Therapeutic Patents Volume 15, 2005 - Issue 5
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Review

Interleukin-2 family cytokines: potential for therapeutic immmunoregulation

Francis J DumontMedor Consulting 421, Dogwood Avenue, Egg Harbor Township, NJ 08234USATel: +1 609 484 2465;E-mail: [email protected]
Pages 521-554 | Published online: 10 May 2005

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  • •• Up-to-date review of the role of IL-7 in thesurvival and homeostasis of naive and memory T cells.
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  • • An up-to-date review of the biology of IL-9 and its receptor.
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  • • Excellent review of the biology of IL-9 and its role in allergic diseases.
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  • BUDAGIAN V, BULANOVA E, ORINSKA Z et al.: Reverse signaling through membrane-bound interleukin-15. J. Biol. Chem. (2004) 279:42192-42201. Provides evidence that membrane-bound IL-15 can signal via MAPK to induce the production of several pro-inflammatory cytokines by human monocytes.
  • NEELY GG, EPELMAN S, MA LL et al.: Monocyte surface-bound IL-15 can function as an activating receptor and participate in reverse signaling. J. Immunol (2004) 172:4225–4234.
  • • Shows that membrane-bound IL-15 can function as a receptor and participate in reverse signalling that results in cellular adhesion and production of inflammatory cytokines in human monocytes.
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  • •• This important study demonstrates that IL-15Ra expressed on monocytes captures and presents IL-15 to neighboring cells in trans through cell-cell contact.
  • PARK CS, YOON SO, ARMITAGE RJ, CHOI YS: Follicular dendritic cells produce IL-15 that enhances germinal center B cell proliferation in membrane-bound form. Immunol (2004) 173:6676–6683.
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  • •• This important study demonstrates that IL-15Rá expressed on monocytes captures and presents IL-15 to neighboring cells in trans through cell-cell contact.
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  • • A review of the role of IL-15 in the homeostasis of NK cells and T cells.
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  • SCHLUNS KS, NOWAK EC, CABRERA-HERNANDEZ A et aL: Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor a expression. Proc. Natl Acad. Sci. USA (2004) 101:5616–5621.
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  • MIN SY, HWANG SY, JUNG YO et al: Increase of cyclooxygenase-2 expression by interleukin-15 in rheumatoid synoviocytes. Rheumatol (2004) 31:875–883.
  • MCINNES IB, GRACIE JA: Interleukin-15: a new cytokine target for the treatment of inflammatory diseases. Curr. Opin. PharmacoL (2004) 4:392–397.
  • •• Review of the data suggesting that IL-15may be involved in pathogenesis of several inflammatory diseases.
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  • • Reviews the biology of IL-21.
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  • • Reviews the biology of IL-21.
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  • •• This paper presents the first indication that IL-21 may participate in a human inflammatory disease.
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  • • Shows that, in humans, IL-21 may be involved in the activation of innate and TH1 immune responses.
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  • • Shows that IL-21 allows the induction of full maturation of human NK cells in vitro.
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  • • This study demonstrates that IL-21 specifically induces the production of IgG1 and IgG3 by CD40-activated naive human B cells.
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  • • Update of the role of IL-2 in the treatment of renal cell carcinoma.
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  • •• Describes the generation and biologicalactivity of Bay 50–4798.
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  • • Compares the abilities of IL-2, IL-15 and IL-21 to stimulate immunity against tumours and shows that IL-21 is superior in sustaining CD8* T cell numbers long term.
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  • • Reviews the effects of IL-7 and IL-15 on lymphopoiesis and the potential use of these cytokines for the treatment of immunodeficiency.
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  • •• This study demonstrates that IL-7stimulates HIV-1 replication from resting CD4* T lymphocytes, suggesting that IL-7 in combination with HAART may help purging viral reservoirs.
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  • • Shows that, following booster immunisation to tetanus toxoid or influenza, CD8* T cell responses are enhanced by IL-15 administration, but not by IL-2 administration.
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  • • Shows that IL-15 promotes the development of DCs that induce potent T111 and Tcl responses in vivo, which might be potentially useful for the immunotherapy of tumors and infectious diseases.
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