interleukin-8 and HTLV-I-Infections

The human T-cell leukemia virus type 1 (HTLV-1) is present throughout the world and is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory conditions. The pathogenesis of HAM/TSP involves a chronic inflammatory response in central nervous system (CNS), with the presence of HTLV-1 infected cells and HTLV-1-specific CD8+ lymphocytes. Chemokines may have a role in the infiltration of these cells into the CNS. In this context, the present study analyzed the level of plasmatic chemokines CCL2 (MCP-1), CCL5 (RANTES), IL8 (CXCL8), CXCL9 (MIG), and CXCL10 (IP-10) and HTLV-1 proviral load from peripheral blood in 162 asymptomatic carriers and 136 HAM/TSP patients to determine the differences that be associated with the clinical status of the HTLV-1 infection. The results showed that patients with HAM/TSP have significantly higher levels of IL8 and CXCL9, and that the level of IL8, CXCL9 and CXCL10 was significantly greater in HTLV-1 infected individuals with high (>1%) than those with low proviral load (<1%). However, the levels of the chemokines tested have not showed high sensitivity to discriminate HAM/TSP patients from asymptomatic carriers. In addition, chemokine profiles in asymptomatic carriers and HAM/TSP groups were similar, with no significant increased frequency of higher producers of chemokines in HAM/TSP individuals. Results indicate that the heterogeneity of the individuals in the groups regarding time of infection, duration of disease, proviral load level and other possible confound factors may impair the use of chemokines levels to monitor HTLV-1 carriers in clinical practice. J. Med. Virol. 88:1438-1447, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Adult; Aged; Asymptomatic Infections; Carrier State; Chemokine CCL2; Chemokine CXCL9; Chemokines; Cohort Studies; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Interleukin-8; Male; Middle Aged; Paraparesis, Tropical Spastic; Viral Load; Young Adult

Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4(+) lymphocytes and is thought to modify their function and a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on diffuse pan-bronchiolitis (DPB), a chronic inflammatory lung disease with infiltration of lymphocytes and hyperplasia of the bronchus-associated lymphoid tissue. In this study, 35 DPB patients with and without HTLV-I infection were examined. HTLV-I positive DPB patients were likely to have a larger affected area with lower FEV(1). The CD3(+)/CD25(+) lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients than in negative patients. MIP-1 alpha, IP-10 and levels in BALF were also significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive patients, the MIP-1 alpha and IP-10 levels showed a significant positive correlation with the percentage of CD3(+)/CD25 lymphocytes. BALF cells of all HTLV-I positive DPB patients showed expression of p40(tax) mRNA. We suggest that HTLV-I infection may modify DPB pathogenesis via activation of T cells. We also found that the frequency of ATL development in HTLV-I positive DPB patients was significantly higher than in all HTLV-I positive patients (OR = 8.22, 95% CI = 2.61-25.9, P < 0.01). The levels of TGF-beta in patients who developed ATL were significantly lower than in patients who did not develop ATL. Sensitivity and specificity were 80% and 85.7%, respectively (cut-off = 20 pg/ml). We also propose that these features should be taken into consideration in the treatment of DPB in HTLV-I infected individuals.

Topics: Adult; Aged; Bronchiolitis; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Chemokine CCL2; Chemokine CCL4; Chemokine CXCL10; Chi-Square Distribution; Chronic Disease; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Interleukin-8; Lymphocyte Activation; Macrophage Inflammatory Proteins; Male; Middle Aged; Prevalence; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric; Transforming Growth Factor beta

Human cytomegalovirus (HCMV) is one of the most frequent opportunistic agents causing severe illness in chronic human T cell leukemia-lymphoma virus type I (HTLV-I) infection. Our previous studies have shown that coinfection of macrophages with HCMV and HTLV-I significantly enhances HCMV replication, resulting in release of infectious HCMV from dually infected cells. We found that double infection of macrophages with HCMV and HTLV-I induced a rapid production of substantial amounts of interleukin-8 (IL-8) and transforming growth factor-beta1 (TGF-beta1). Results of transfection studies demonstrated that the tax gene product of HTLV-I was able to induce secretion of IL-8 and TGF-beta1. In addition to its cytokine-inducing effect, the Tax protein could interact with HCMV synergistically to result in production of much higher levels of IL-8 and TGF-beta1 than expected on the basis of their separate activities. Treatment of dually infected macrophage cultures with neutralizing antibodies to IL-8 and TGF-beta1 led to a nearly 1000-fold decrease in release of infectious HCMV from coinfected cells. Similar results were obtained when anti-IL-8 and anti-TGF-beta1 treatments were combined in macrophage cultures transfected with the tax gene before HCMV infection. Our results suggest that the stimulatory effect of HTLV-I Tax protein on HCMV replication in coinfected macrophages is largely mediated by high levels of IL-8 and TGF-beta1 production.

Topics: Antibodies, Monoclonal; Cell Line; Cytomegalovirus Infections; Gene Products, tax; HTLV-I Infections; Humans; Interleukin-8; Macrophages; Transforming Growth Factor beta; Virus Replication

The culture supernatants from 43 human cell lines obtained during log phase and from purified normal peripheral blood B-lymphocytes cultured at 10(6) cells ml-1 for 48 h in RPMI 1640-5% fetal calf serum were examined for interleukin-8 (IL-8) using Elisa kits. Constitutive IL-8 production was found for 14/15 B-cell lines (5 derived from normal persons and 2 from AML patients, 1 pre-B-ALL, 2 CLL with trisomy 12, 2 HTLV-I+, 1 HTLV-II+, 1/2 Burkitt lymphoma), 4/16 T-cell lines (3/6 HTLV-I+, 1 HTLV-II+, 0/9 T-ALL), myeloid line HL-60, monocytoid line U937, 3/3 ovarian carcinoma, 1/1 endometriosis, 2/2 normal fibroblast, 0/2 C-ALL, 0/1 pre-erythroid line K562, as well as for normal B-lymphocytes. Later, cells examined by indirect immunofluorescence using IL-8 antibodies gave a positive reaction. DNA from 4 IL-8 producing and 3 non-producing cell lines, when probed with IL-8 cDNA gave the same 3.5 kb EcoRI fragment indicating similarities of the IL-8 gene in these cells. Two B-cell lines examined showed the expression of 1.8 kb IL-8 mRNA. These results indicate IL-8 production by a greater variety of cells than previously believed which open possibilities for new IL-8-mediated immune functions by such cells as B-cells.

Topics: B-Lymphocytes; Blotting, Southern; Burkitt Lymphoma; Cell Line; DNA Probes; Enzyme-Linked Immunosorbent Assay; HTLV-I Infections; HTLV-II Infections; Humans; Interleukin-8; Leukemia; Reference Values; T-Lymphocytes; Tumor Cells, Cultured