title: Involvement of interleukin-18 in acute graft-versus-host disease in mice.
abstract: BACKGROUND
  Interleukin (IL)-18 stimulates T helper 1 (Th1)-mediated immune responses and the development of cytotoxic T lymphocytes (CTLs). Antihost CTLs are major effectors in acute graft-versus-host disease (aGvHD), a potentially fatal complication after allogeneic stem-cell transplantation. We investigated the relevant role of IL-18 in the development of aGvHD in mice.
  
  
  METHODS
  Irradiated (C57BL/6x DBA/2) F1 (BDF1) mice transplanted with wild-type (WT) C57BL/6 (B6) splenocytes were compared with those transplanted with IL-18Ralpha-deficient B6 splenocytes with respect to Th1 development, CTL activity, severity of aGvHD, and survival.
  
  
  RESULTS
  Transplantation of WT B6 spleen cells into BDF1 mice induced aGvHD that was accompanied by elevation of both serum IL-18 levels and IL-18 receptor alpha chain (IL-18Ralpha) expression on engrafted T cells. The transplantation of WT B6 cells also induced high antihost CTL activity in host spleen, whereas transplantation of IL-18Ralpha-deficient B6 cells exhibited significantly reduced antihost-specific CTL activity, indicating that IL-18Ralpha-deficient CTLs were less cytotoxic than IL-18Ralpha-expressing CTLs. Moreover, the hosts receiving transplants with the IL-18Ralpha-deficient B6 cells had fewer fatal tissue injuries and increased their survival rates as compared with those receiving transplants with WT cells. Nevertheless, Th1 development in the hosts was the same, regardless of the type of donor cells.
  
  
  CONCLUSIONS
  These results suggest that Th1 induction and baseline CTL activity in aGvHD occur in the absence of IL-18, but endogenous IL-18 further accelerates aGvHD reaction to its full-blown manifestation. Thus, IL-18 may be involved in the development aGvHD by enhancing CTL activity.
authors.affiliation: Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Itoi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsui
authors.forename: Ayako
authors.initials: A
authors.lastname: Sugihara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Terada
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hada
authors.forename: Eizo
authors.initials: E
authors.lastname: Kakishita
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D000208:Acute Disease; D000818:Animals; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D020382:Interleukin-18 / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018123:Receptors, Interleukin / Q000502:physiology; D053724:Receptors, Interleukin-18; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18