title: Elevation of activated platelet-dependent chemokines and soluble cell adhesion molecules in patients with hematologic malignancies and high levels of beta-D-glucan.
abstract: Most invasive fungal infections such as candidemia are frequent in patients with hematologic malignancies. We measured cytokines/chemokines (IL-6, IL-8, monocytic chemoattractant protein 1, RANTES and epithelial neutrophil-activating peptide 78), soluble molecules (sFas, sE-selectin and soluble vascular cell adhesion molecule 1) and platelet activation markers (soluble CD40 ligand, sP-selectin and platelet-derived microparticles) in patients with hematologic malignancies under prophylactic treatment with an antifungal drug (fosfluconazole). We classified patients into 2 groups by the level of beta-D-glucan. The level of C-reactive protein was higher in the high beta-D-glucan group (>5 pg/ml) than in the low beta-D-glucan group. However, there were no differences in the levels of other parameters (peripheral blood cells, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, blood urea nitrogen and creatinine). Patients in the high beta-D-glucan group exhibited a significant elevation of several chemokines, soluble molecules and platelet activation markers compared with those in the low beta-D-glucan group, but the levels of IL-8, monocytic chemoattractant protein 1 and sFas did not differ significantly. The levels of C-reactive protein and IL-6 increased significantly after 1 or 2 weeks on fosfluconazole in both groups. In contrast, the high beta-D-glucan group exhibited a significant decrease in chemokines, soluble markers and platelet-derived microparticles compared with the low beta-D-glucan group after treatment with fosfluconazole, although the patients in the low beta-D-glucan group exhibited no significant changes. Furthermore, the levels of RANTES, epithelial neutrophil-activating peptide 78, soluble vascular cell adhesion molecule 1 and sE-selectin correlated positively with platelet-derived microparticles in the high beta-D-glucan group. These findings suggest that fungal infection may modulate the vascular events in which some platelet-related chemokines are involved.
authors.affiliation: Division of Hematology, Kishiwada City Hospital, Kishiwada, Japan. shosaku-n@mbp.ocn.ne.jp
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Iishii
authors.forename: N
authors.initials: N
authors.lastname: Inami
authors.forename: E
authors.initials: E
authors.lastname: Kimura
authors.forename: F
authors.initials: F
authors.lastname: Urase
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D002177:Candidiasis / Q000097:blood / Q000175:diagnosis; D015815:Cell Adhesion Molecules / Q000097:blood*; D018925:Chemokines / Q000097:blood*; D005260:Female; D015725:Fluconazole / Q000031:analogs & derivatives / Q000627:therapeutic use; D016469:Fungemia / Q000097:blood* / Q000150:complications / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010755:Organophosphates / Q000627:therapeutic use; D015539:Platelet Activation; D011355:Prodrugs / Q000627:therapeutic use; D047071:beta-Glucans / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018925:Chemokines; D010755:Organophosphates; D011355:Prodrugs; D047071:beta-Glucans; C486878:fosfluconazole; D015725:Fluconazole