title: Elevated HMGB1-related interleukin-6 is associated with dynamic responses of monocytes in patients with active pulmonary tuberculosis.
abstract: There were limited studies assessing the role of HMGB1 in TB infection. In this prospective study, we aimed to assess the levels of HMGB1 in plasma or sputum from active pulmonary tuberculosis (APTB) patients positive for Mtb culture test, and to evaluate its relationship with inflammatory cytokines and innate immune cells. A total of 36 sputum Mtb culture positive APTB patients and 32 healthy volunteers (HV) were included. Differentiated THP-1 cells were treated for 6, 12 and 24 hrs with BCG at a multiplicity of infection of 10. The absolute values and percentages of white blood cells (WBC), neutrophils, lymphocytes, and monocytes were detected by an automatic blood analyzer. Levels of HMGB1, IL-6, IL-10 and TNF-α in plasma, sputum, or cell culture supernatant were measured by ELISA. The blood levels of HMGB1, IL-6, IL-10 and TNF-α, the absolute values of WBC, monocytes and neutrophils, and the percentage of monocytes were significant higher in APTB patients than those in HV groups (P < 0.05). The sputum levels of HMGB1, IL-10, and TNF-α were also significantly higher in APTB patients than those in HV groups (P < 0.05). Meanwhile, plasma level of HMGB1, IL-6, and IL-10 in APTB patients were positively correlated with those in sputum (P < 0.05), respectively. IL-6 was positively correlated with HMGB1 both in plasma and sputum of APTB patients (P < 0.05). HMGB1 and IL-6 is positively correlated with the absolute number of monocytes in APTB patients (P < 0.05). BCG induced HMGB1, IL-6, IL-10 and TNF-α production effectively in PMA-treated THP-1 cells. HMGB1 may be used as an attractive biomarker for APTB diagnosis and prognosis and may reflect the inflammatory status of monocytes in patients with APTB.
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics 1 Xincheng Road, Dongguan 523808, People's Republic of China ; Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College No. 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Jin-Cheng
authors.initials: JC
authors.lastname: Zeng
authors.affiliation: Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College No. 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Xiang
authors.affiliation: Dongguan 6th People's Hospital Dongguan 523008, People's Republic of China.
authors.forename: Dong-Zi
authors.initials: DZ
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Jun-Ai
authors.initials: JA
authors.lastname: Zhang
authors.affiliation: Dongguan 6th People's Hospital Dongguan 523008, People's Republic of China.
authors.forename: Gan-Bin
authors.initials: GB
authors.lastname: Liu
authors.affiliation: Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College No. 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College No. 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Gao
authors.affiliation: Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College No. 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, Affiliated Hospital of Guangdong Medical College Zhanjiang 524001, People's Republic of China.
authors.forename: Xian-Jing
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Dongguan 6th People's Hospital Dongguan 523008, People's Republic of China.
authors.forename: Lai-Long
authors.initials: LL
authors.lastname: Yi
authors.affiliation: Division of Cardiovascular Medicine, University of Maryland School of Medicine Maryland 21201, USA.
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Zhong
authors.affiliation: Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics 1 Xincheng Road, Dongguan 523808, People's Republic of China ; Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College No. 1 Xincheng Road, Dongguan 523808, People's Republic of China.
authors.forename: Jun-Fa
authors.initials: JF
authors.lastname: Xu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D024243:HMGB1 Protein / Q000032:analysis* / Q000097:blood; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis* / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011379:Prognosis; D013183:Sputum / Q000737:chemistry*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C508609:IL10 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Active pulmonary tuberculosis; HMGB1; cytokines; immunity; infection