Expression of Th2 cytokines decreases the development of and improves Behçet's disease-like symptoms induced by herpes simplex virus in mice.

In the etiology of Behçet's disease (BD), viral infection has long been postulated as a contributing factor, and viral involvement has been demonstrated. However, viral infection alone is not sufficient to explain the pathogenesis of BD, and some evidence suggests that immunologic abnormalities are also important. To study the possible role of immune regulation in the development of BD-like symptoms induced by herpes simplex virus inoculation in ICR mice, macrophages were deleted by use of liposome-encapsulated clodronate (lip-Cl(2)MDP). Treatment with lip-Cl(2)MDP suppressed the development of BD-like symptoms, and this suppression was correlated with the induction of interleukin-4 expression in mouse spleens. When the Th2 adjuvant ovalbumin (OVA)-alum was injected into mice with BD-like symptoms, their cutaneous symptoms improved. Adoptive transfer with splenocytes from OVA-alum-injected mice also resulted in improvement. These findings suggest that up-regulated Th2 cytokine expression can attenuate the development of and improve some BD-like symptoms.

[1]  T. Lehner Immunopathogenesis of Behçet's disease. , 1999, Annales de medecine interne.

[2]  H. Jun,et al.  Absolute requirement of macrophages for the development and activation of beta-cell cytotoxic CD8+ T-cells in T-cell receptor transgenic NOD mice. , 1999, Diabetes.

[3]  Y. Nishiyama,et al.  The role of polymorphonuclear leukocyte infiltration in herpes simplex virus infection of murine skin , 1999, Archives of Dermatological Research.

[4]  T. Lehner,et al.  HSP-derived peptides inducing uveitis and IgG and IgA antibodies. , 1998, Experimental eye research.

[5]  E. Yılmaz,et al.  The Levels of Plasma Interleukin‐2 and Soluble Interleukin‐2R in Behçet's Disease: A Marker of Disease Activity , 1998, The Journal of dermatology.

[6]  W. Fiers,et al.  Macrophages induce cellular immunity by activating Th1 cell responses and suppressing Th2 cell responses. , 1998, Journal of immunology.

[7]  Hirohata,et al.  Abnormal T cell responses to bacterial superantigens in Behçet's disease (BD) , 1998, Clinical and experimental immunology.

[8]  S. Ohno,et al.  Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet's disease. , 1998, Investigative ophthalmology & visual science.

[9]  S. Al-Sedairy,et al.  Divergent cytokine production profile in Behçet's disease. Altered Th1/Th2 cell cytokine pattern. , 1998, The Journal of rheumatology.

[10]  Eun-So Lee,et al.  Behçet's disease-like symptoms induced by the Herpes simplex virus in ICR mice. , 1998, European journal of dermatology : EJD.

[11]  Douglas,et al.  Neither interleukin‐6 nor signalling via tumour necrosis factor receptor‐1 contribute to the adjuvant activity of Alum and Freund’s adjuvant , 1998, Immunology.

[12]  L. Emmi,et al.  Pathogenesis and therapy of Behçet's disease. , 1997, Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna.

[13]  P. Villiger,et al.  Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechçet's disease; soluble TNFR-75 as a biological marker of disease activity. , 1997, The Journal of rheumatology.

[14]  H. Bluethmann,et al.  In interleukin‐4‐deficient mice, alum not only generates T helper 1 responses equivalent to Freund's complete adjuvant, but continues to induce T helper 2 cytokine production , 1996, European journal of immunology.

[15]  R. Goodman,et al.  In vivo depletion of CD8+ T cells results in Th2 cytokine production and alternate mechanisms of allograft rejection. , 1995 .

[16]  K. Gyo,et al.  Experimental vestibular neuritis induced by herpes simplex virus. , 1993, Acta oto-laryngologica. Supplementum.

[17]  W. Paul,et al.  The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice , 1992, The Journal of experimental medicine.

[18]  T. Lehner,et al.  Detection of HSV-1 DNA in patients with Behçet's syndrome and in patients with recurrent oral ulcers by the polymerase chain reaction. , 1991, Journal of medical microbiology.

[19]  T. Mosmann,et al.  Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. , 1990, Science.

[20]  Lesley J. Murray,et al.  In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp‐lpr/lpr mouse , 1990, European journal of immunology.

[21]  N. Rooijen The liposome-mediated macrophage ‘suicide’ technique , 1989 .

[22]  N. Van Rooijen The liposome-mediated macrophage 'suicide' technique. , 1989, Journal of immunological methods.

[23]  A. Denman,et al.  Treatment with acyclovir does not affect orogenital ulcers in Behçet's syndrome: a randomized double-blind trial. , 1988, British journal of rheumatology.

[24]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[25]  K. Namba,et al.  Behçet's disease and streptococcal infection. , 1986, Japanese journal of ophthalmology.

[26]  K. Arai,et al.  Use of a cDNA expression vector for isolation of mouse interleukin 2 cDNA clones: expression of T-cell growth-factor activity after transfection of monkey cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[27]  G. Trinchieri,et al.  Human natural killer cells: biologic and pathologic aspects. , 1984, Laboratory investigation; a journal of technical methods and pathology.

[28]  T. Lehner,et al.  DETECTION OF RNA COMPLEMENTARY TO HERPES-SIMPLEX VIRUS IN MONONUCLEAR CELLS FROM PATIENTS WITH BEHÇET'S SYNDROME AND RECURRENT ORAL ULCERS , 1982, The Lancet.

[29]  S. Miyazawa,et al.  EXPERIMENTAL BEHÇET'S DISEASE AND ULTRASTRUCTURAL X‐RAY MICROANALYSIS OF PATHOLOGICAL TISSUES , 1979, The Journal of dermatology.

[30]  K. Aoki,et al.  Specific histocompatibility antigens associated with Behçet's disease. , 1975, American journal of ophthalmology.

[31]  T. Lehner Behçet's syndrome and autoimmunity. , 1967, British medical journal.

[32]  F. Sezer The isolation of a virus as the cause of Behcet's diseases. , 1953, American journal of ophthalmology-glaucoma.

[33]  H. Behcet UBER REZIDIVERENDE APHTHOSE DURCH EIN VIRUS VERURSACHTE GESCHWURE AM MUND, AM AUGE UND AN DEN GENITALIEN , 1937 .