Elevated Serum Levels of CCL17 Correlate with Increased Peripheral Blood Platelet Count in Patients with Active Tuberculosis in China

Abstract

Active tuberculosis (TB) has been associated with imbalance of Th1 and Th2 cytokine pattern. Activation of Th1 lymphocytes, gamma interferon (IFN-␥) production and macrophage activation are crucial in defense against mycobacteria, while Th2 activation and interleukin-4 (IL-4) production are associated with TB progressing and with poor clinical outcome after treatment (6).After being secreted, IFN-␥ and IL-4 are rapidly bound by their receptors and/or inactivated by proteases, which leads to difficulty in detecting these two typical Th1/Th2 cytokines in plasma or serum (26). Therefore, other markers have been investigated as alternative indicators of preferential Th1 or Th2 activity in vivo.CCL17 (thymus and activation-regulated chemokine [TARC]) and CCL22 (macrophage-derived chemokine [MDC]) are two specific chemotactic factors for Th2 cells (12). CD30, a tumor necrosis factor (TNF) receptor II family member, is also correlated with Th2 activation (3). sCD30 is a soluble form of CD30, which is generated by proteolytic cleavage of the extracellular portion of this transmembrane molecule and can be measured in serum or plasma by enzyme-linked immunosorbent assay (ELISA). Previous reports indicate increasing expression of these factors in patients with Th2 bias status, such as asthma (27), arthritis (7), and lymphoma (2); however, very few reports examine the changes in these Th2 factors in TB patients (16).For screening of new Th2 markers in active TB patients, we compared the serum levels of CCL17/TARC, CCL22/MDC, and sCD30 in HIV-negative TB patients with samples obtained from community healthy controls in China. The results indicate that CCL17/TARC and sCD30 might be more suitable as serum Th2 marker than CCL22/MDC in active TB patients. The correlation of these Th2 markers and the platelet and eosinophil counts in peripheral blood were also analyzed. MATERIALS AND METHODSStudy subjects. Peripheral blood was obtained from 103 normal healthy subjects, 101 active pulmonary TB patients, and 18 TB patients in recovery. The age and sex information of patients and controls are presented in Table 1. The patients included were clinically and radiologically diagnosed for pulmonary TB, and diagnoses confirmed by sputum smear and culture for Mycobacterium tuberculosis. The patients were recruited from the clinics of Shanghai Pulmonary Hospital. All of the patients were HIV negative; none of them presented with other infectious diseases or immunosuppressive conditions. All of the active TB patients received anti-TB therapy for less than 1 week and were classified into three categories (5): mild TB was defined by the presence of scattered and nonconfluent pulmonary infiltrates of slight to moderate density in one or both lungs, with the total volume less than one lung, without cavities. Moderate TB was defined by scattered and nonconfluent pulmonary infiltrates present in one or both lungs and/or with dense and confluent lesions but not involving more than one-third of the volume of one lung, with or without cavities with a...

Mean platelet volume as an inflammation marker in active pulmonary tuberculosis

“…Similarly, Baynes et al [25] found the MPV to be low in patients with active PTB and suggested that although thrombopoiesis increased in patients with TB, the platelets’ lifetime may have been shortened. Platelets and their indices in active PTB have been addressed in several previous studies [6,26,27,32]. Contrary to our study, Tozkoparan et al [6] found that the MPV was significantly higher in patients with active TB than in control patients with inactive TB and non-specific pneumonia and decreased with anti-TB treatment.…”

Comparison of platelet count in tuberculosis spine to other spine pathology

“…TH1 is essential for the attack against intracellular mycobacterium tuberculosis while TH2 has been associated with a poor clinical outcome [20] Cytokine CCL7 is released by platelets causing an increase in TH-2 activity as illustrated by Feng et al [22]. Platelet count may therefore have prognostic value in the long term and further research needs to be implemented.…”

Cytokines and Chemokines inMycobacterium tuberculosisInfection

“…In the context of Mtb infection, T REG are increased in the peripheral blood of TB patients and inhibit production of IFNγ by Mtb-specific CD4 + T cells (393, 394) and CCR4 antagonists promote proliferation of T cells during MVA85A vaccination (395). The ligand for CCR4, CCL17 but not CCL22 has also been shown to be elevated in the serum of active TB patients (396). These data suggest that CCR4 mediated regulation of T cell responses to Mtb antigens may occur during TB and that antagonism of CCR4 maybe a target for therapeutic use or as an adjuvant during vaccination.…”