Heparin-binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients

Stjärne Aspelund, Anna; Hammarström, Helena; Inghammar, Malin; Larsson, Hillevi; Hansson, Lennart; Christensson, Bertil; Påhlman, Lisa I.

can therefore be difficult to distinguish clinically. However, Lntx patients may lack classical signs of infection due to heavy immunosuppression, and rejection may be asymptomatic. In addition, there are possible links between infection and the development of rejection. 4 For example, viral pneumonia has been associated with chronic lung allograft dysfunction and graft loss. 5 Antimicrobial peptides in respiratory secretions play an important role as a first line of defence against infections. 7 Lysozyme is the most abundant airway antimicrobial peptide, and is secreted primarily by neutrophils and sub-mucosal glands. 8 Heparin-binding protein (HBP) was initially recognized for its broad antimicrobial activity, but is now known to be a multifunctional inflammatory mediator that induces vascular leakage and acts as a chemoattractant and activator of monocytes. 9, 10 The protein is stored in secretory and azurophilic granules of neutrophils, and is rapidly released upon cell activation. 11 Plasma HBP has been described as a promising biomarker for severe sepsis and septic shock, 12 and elevated HBP levels have also been shown in cerebrospinal fluid during bacterial meningitis 13 and in urine during urinary tract infections. 14 Neither HBP nor lysozyme has previously been evaluated in BALF of Lntx patients. In this study, we quantified the two proteins together with the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8 and TNF, and anti-inflammatory IL-10 in BALF collected during the first year after transplantation. The primary aim was to evaluate HBP and lysozyme as potential biomarkers for infection, and to determine their ability to discriminate infection from rejection in lung transplant recipients.