Tumour necrosis factor-α production during cytomegalovirus infection in immunosuppressed rats

The production of tumour necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6, all proinflammatory cytokines, was investigated in radiation-immunosuppressed rats infected with rat cytomegalovirus (RCMV). At day 7 post-infection, when the animals showed disease signs, high TNF-α levels were detected in the serum and in homogenates of various organ tissues. In contrast, IL-1 and IL-6 levels were not significantly elevated. Moreover, replication of RCMV induced TNF-α expression in different types of cells grown in vitro. When frozen tissue sections were examined by immunohistology, TNF-α-producing cells were found in areas with extensive pathology in the lungs, spleen and liver. Both lymphocytes and RCMV-infected cells were identified as the sources of TNF-α. Its abundance in RCMV-infected rats suggests an important role for TNF-α in CMV pathogenesis.

[1]  T. Espevik,et al.  A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. , 1986, Journal of immunological methods.

[2]  Jiahuai Han,et al.  Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level [published erratum appears in J Exp Med 1990 Mar 1;171(3):971-2] , 1990, The Journal of experimental medicine.

[3]  J. Shanley,et al.  IS CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS IN TRANSPLANT RECIPIENTS AN IMMUNOPATHOLOGICAL CONDITION? , 1987, The Lancet.

[4]  P. Vassalli,et al.  The pathophysiology of tumor necrosis factors. , 1992, Annual review of immunology.

[5]  R. Chanock,et al.  A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Goeddel,et al.  Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. , 1986, Nature.

[7]  Marian C. Horzinek,et al.  Tumor necrosis factor alpha promotes replication and pathogenicity of rat cytomegalovirus , 1994, Journal of virology.

[8]  C. Dinarello Interleukin-1 and its biologically related cytokines. , 1989, Advances in immunology.

[9]  E. Claassen,et al.  In vivo kinetics and characterization of IFN-gamma-producing cells during a thymus-independent immune response. , 1991, Journal of immunology.

[10]  L. F. Fajardo,et al.  Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. , 1987, Science.

[11]  M. Raffeld,et al.  Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. , 1992, The Journal of clinical investigation.

[12]  D. Hallahan,et al.  Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Moore,et al.  Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Marian C. Horzinek,et al.  Tumour necrosis factor α, interferon γ and interferon β exert antiviral activity in nervous tissue cells , 1991 .

[15]  L. Aarden,et al.  Functional discrimination between interleukin 6 and interleukin 1 , 1988, European journal of immunology.

[16]  J. Snick,et al.  Interleukin-6: an overview. , 1990, Annual review of immunology.

[17]  D. Longo,et al.  Death in the AIDS patient: role of cytomegalovirus. , 1983, The New England journal of medicine.

[18]  R. Schreiber,et al.  Generation and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors. , 1989, Journal of immunology.

[19]  M. Ho,et al.  Cytomegalovirus: Biology and Infection , 1982 .

[20]  B. Beutler,et al.  CACHECTIN: MORE THAN A TUMOR NECROSIS FACTOR , 1988 .

[21]  A. Billiau Redefining interferon: the interferon-like antiviral effects of certain cytokines (interleukin-1, interferon-beta 2, interferon-gamma) may be indirect or side effects. , 1987, Antiviral research.

[22]  H. Holtmann,et al.  Tumor necrosis factor induction by Sendai virus. , 1986, Journal of immunology.

[23]  M. Ho Human Cytomegalovirus Infections in Immunosuppressed Patients , 1991 .

[24]  N. Flournoy,et al.  Risk factors for cytomegalovirus infection after human marrow transplantation. , 1986, The Journal of infectious diseases.

[25]  H. Tilg,et al.  Cachexia and tumour necrosis factor-alpha in cytomegalovirus infection. , 1991, Journal of clinical pathology.

[26]  J. D. Albert,et al.  Shock and tissue injury induced by recombinant human cachectin. , 1986, Science.

[27]  H. Romijn,et al.  Culture of rat cerebral oligodendrocytes in a serum-free, chemically defined medium , 1984, Journal of Neuroscience Methods.

[28]  E. Huang,et al.  Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes. , 1989, Journal of immunology.

[29]  C. Herzog,et al.  [Interleukin 1 and tumor necrosis factor]. , 1987, Zeitschrift fur Rheumatologie.

[30]  L. Cone,et al.  Cytomegalovirus viremia increases with progressive immune deficiency in patients infected with HTLV-III. , 1986, AIDS research.