Human cytomegalovirus infection in lung transplant recipients triggers a CXCL-10 response

Am J Transplant. 2011 Mar;11(3):542-52. doi: 10.1111/j.1600-6143.2010.03404.x. Epub 2011 Jan 10.

Abstract

Human cytomegalovirus (HCMV) causes significant morbidity in lung transplant recipients (LTRs). The clinical effects of HCMV replication are determined partly by a type 1 T-helper cell (Th1) response. Because the chemokine interferon-inducible protein of 10 kilodaltons (IP-10, CXCL-10) induces a Th1 response, we investigated whether HCMV triggers IP-10 in LTRs. The IP-10 concentration and HCMV DNA load were determined in 107 plasma and 46 bronchoalveolar lavage fluid (BALF) samples from 36 LTRs. Initial HCMV detection posttransplantation was significantly associated with increased plasma IP-10, regardless of whether the patients showed HCMV DNAemia (p = 0.001) or HCMV replication only in the allograft (p < 0.0001). In subsequent episodes of HCMV detection, plasma IP-10 increased regardless of whether HCMV was detected in blood (p = 0.0078) or only in BALF (p < 0.0001) and decreased after successful antiviral therapy (p = 0.0005). Furthermore, levels of HCMV DNA and IP-10 correlated statistically (p = 0.0033). Increased IP-10 levels in HCMV-positive BALF samples were significantly associated with severe airflow obstruction, as indicated by a decrease in forced expiratory volume in one second (FEV1). Our data indicate that HCMV replication in LTRs evokes a plasma IP-10 response and that, when an IP-10 response is observed in BALF, it is associated with inflammatory airway obstruction in the allograft.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Bronchoalveolar Lavage Fluid / virology*
  • Chemokine CXCL10 / blood
  • Cytomegalovirus / genetics
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / virology*
  • DNA, Viral / genetics
  • Female
  • Humans
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications*
  • Retrospective Studies
  • Risk Factors
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • CXCL10 protein, human
  • Chemokine CXCL10
  • DNA, Viral