A defective type 1 response to rhinovirus in atopic asthma

Background: Rhinoviruses (RVs) are the most frequent precipitants of the common cold and asthma exacerbations, but little is known about the immune response to these viruses and its potential implications in the pathogenesis of asthma. Methods: Peripheral blood mononuclear cells (PBMC) from patients with atopic asthma and normal subjects were exposed to live or inactivated RV preparations. Levels of interferon (IFN)γ and interleukins IL-12, IL-10, IL-4, IL-5 and IL-13 were evaluated in the culture supernatants with specific immunoassays. Results: Exposure of PBMC to RVs induced the production of IFNγ, IL-12, IL-10, and IL-13. Cells from asthmatic subjects produced significantly lower levels of IFNγ and IL-12 and higher levels of IL-10 than normal subjects. IL-4 was induced only in the asthmatic group, while the IFNγ/IL-4 ratio was more than three times lower in the asthmatic group. Conclusions: This evidence suggests that the immune response to RVs is not uniquely of a type 1 phenotype, as previously suggested. The type 1 response is defective in atopic asthmatic individuals, with a shift towards a type 2 phenotype in a way similar, but not identical, to their aberrant response to allergens. A defective type 1 immune response to RVs may be implicated in the pathogenesis of virus induced exacerbations of asthma.

[1]  W. Busse,et al.  Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. , 2000, American journal of respiratory and critical care medicine.

[2]  P. Sterk,et al.  Rhinovirus infections: induction and modulation of airways inflammation in asthma , 1999, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[3]  N. Papadopoulos,et al.  Rhinoviruses replicate effectively at lower airway temperatures , 1999, Journal of medical virology.

[4]  J. Altman,et al.  Two Roads Diverged: Interferon α/β– and Interleukin 12–mediated Pathways in Promoting T Cell Interferon γ Responses during Viral Infection , 1999, The Journal of experimental medicine.

[5]  S. Johnston,et al.  Rhinovirus Infection Induces Expression of Its Own Receptor Intercellular Adhesion Molecule 1 (ICAM-1) via Increased NF-κB-mediated Transcription* , 1999, The Journal of Biological Chemistry.

[6]  R. Homer,et al.  Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. , 1999, The Journal of clinical investigation.

[7]  N. Papadopoulos,et al.  The acute exacerbation of asthma: Pathogenesis , 1999 .

[8]  D D Donaldson,et al.  Interleukin-13: central mediator of allergic asthma , 1998 .

[9]  G. Taylor,et al.  Cytokine expression in pulmonary and peripheral blood mononuclear cells from calves infected with bovine respiratory syncytial virus. , 1998, Research in veterinary science.

[10]  D. Strachan,et al.  Prevalence of asthma symptoms, diagnosis, and treatment in 12–14 year old children across Great Britain (international study of asthma and allergies in childhood, ISAAC UK) , 1998, BMJ.

[11]  G. Marone.  Asthma: recent advances. , 1998, Immunology today.

[12]  B. Graham,et al.  Overexpression of interleukin-4 delays virus clearance in mice infected with respiratory syncytial virus , 1997, Journal of virology.

[13]  G. Karupiah,et al.  Cytokines and immunity to viral infections , 1997, Immunological reviews.

[14]  B. Chain,et al.  Characterization of the T cell response to human rhinovirus in children: implications for understanding the immunopathology of the common cold. , 1997, The Journal of infectious diseases.

[15]  S. Romagnani,et al.  The Th1/Th2 paradigm. , 1997, Immunology today.

[16]  L. Borish,et al.  TH1/TH2 lymphocytes: doubt some more. , 1997, The Journal of allergy and clinical immunology.

[17]  S. Johnston,et al.  Rhinoviruses induce interleukin-8 mRNA and protein production in human monocytes. , 1997, The Journal of infectious diseases.

[18]  A. O’Garra,et al.  Th1 and Th2 cytokine induction in pulmonary T cells during infection with respiratory syncytial virus. , 1996, The Journal of general virology.

[19]  W. Busse,et al.  Rhinovirus produces nonspecific activation of lymphocytes through a monocyte-dependent mechanism. , 1996, Journal of immunology.

[20]  S. Wenzel,et al.  Interleukin-10 regulation in normal subjects and patients with asthma. , 1996, Journal of Allergy and Clinical Immunology.

[21]  S. Durham,et al.  Increased interleukin-10 messenger RNA expression in atopic allergy and asthma. , 1996, American journal of respiratory cell and molecular biology.

[22]  J. Orange,et al.  An absolute and restricted requirement for IL-12 in natural killer cell IFN-gamma production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections. , 1996, Journal of immunology.

[23]  W. Busse,et al.  Rhinovirus enters but does not replicate inside monocytes and airway macrophages. , 1996, Journal of immunology.

[24]  R. Silverman,et al.  Respiratory syncytial virus induces interleukin-10 by human alveolar macrophages. Suppression of early cytokine production and implications for incomplete immunity. , 1995, The Journal of clinical investigation.

[25]  S. Johnston.  Natural and experimental rhinovirus infections of the lower respiratory tract. , 1995, American journal of respiratory and critical care medicine.

[26]  D. Proud,et al.  Infection of a human respiratory epithelial cell line with rhinovirus. Induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. , 1995, The Journal of clinical investigation.

[27]  Stephen T Holgate,et al.  Community study of role of viral infections in exacerbations of asthma in 9-11 year old children , 1995, BMJ.

[28]  S. Johnston,et al.  Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects. , 1995, American journal of respiratory and critical care medicine.

[29]  H. Pircher,et al.  Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia , 1995, The Journal of experimental medicine.

[30]  W. Busse,et al.  A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects. , 1994, The Journal of clinical investigation.

[31]  F. Hayden,et al.  Comparative antirhinoviral activities of soluble intercellular adhesion molecule-1 (sICAM-1) and chimeric ICAM-1/immunoglobulin A molecule , 1994, Antimicrobial Agents and Chemotherapy.

[32]  E. Kuechler,et al.  Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Openshaw,et al.  Distinct types of lung disease caused by functional subsets of antiviral T cells , 1994, The Journal of experimental medicine.

[34]  K. Nicholson,et al.  Respiratory viruses and exacerbations of asthma in adults. , 1993, BMJ.

[35]  P. Scott.  IL-12: initiation cytokine for cell-mediated immunity. , 1993, Science.

[36]  D. Horohov,et al.  Rhinovirus induces natural killer‐like cytotoxic cells and interferon alpha in mononuclear leukocytes , 1991, Journal of medical virology.

[37]  J. Hsia,et al.  Peripheral blood mononuclear cell interleukin-2 and interferon-gamma production, cytotoxicity, and antigen-stimulated blastogenesis during experimental rhinovirus infection. , 1990, The Journal of infectious diseases.

[38]  E. Lennette,et al.  Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections , 1989 .

[39]  G. Jackson,et al.  Acute-phase decrease of T lymphocyte subsets in rhinovirus infection. , 1986, The Journal of infectious diseases.