Chest
Volume 124, Issue 6, December 2003, Pages 2283-2292
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Laboratory and Animal Investigations
High Expression of p40tax and Pro-inflammatory Cytokines and Chemokines in the Lungs of Human T-Lymphotropic Virus Type 1-Related Bronchopulmonary Disorders

https://doi.org/10.1378/chest.124.6.2283Get rights and content

Study objective

Human T-lymphotropic virus type 1 (HTLV-1) is closely associated with the development of certain pulmonary diseases, such as bronchiolitis, although the pathologic mechanism remains unclear. To elucidate the pathogenesis of HTLV-1–associated bronchopulmonary disorders, we analyzed the relationship between expression of p40tax, a regulatory component of HTLV-1 that stimulates various host genes, and synthesis of pro-inflammatory cytokines and chemokines by cells in BAL fluid (BALF) obtained from HTLV-1–infected patients.

Design

Reverse transcription-polymerase chain reaction was used to compare the expression of p40tax and pro-inflammatory cytokines and chemokines messenger RNA (mRNA) in BALF of 10 HTLV-1 carriers and 7 healthy subjects. We also studied the correlation between these parameters and the proportion of lymphocytes in BALF.

Results

The expression levels of pro-inflammatory cytokines (interferon [IFN]-γ, interleukin-2) and chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1α, IFN-γ–inducible protein-10 [IP-10]) were significantly higher in BALF of patients than of healthy subjects. The expression of IFN-γ and MIP-1α mRNA correlated with that of p40tax. IFN-γ and IP-10 mRNA expression correlated with the proportion of lymphocytes in BALF. The percentage of lymphocytes in BALF increased with higher expression levels of p40tax mRNA, although the correlation was not significant.

Conclusion

Our results suggested that p40tax seems be involved in the development of HTLV-1–associated bronchopulmonary disorders at least in part through the local production of pro-inflammatory cytokines and chemokines.

Section snippets

Study Subjects

We examined 10 HTLV-1–seropositive individuals with lung lesions and various pulmonary symptoms (1 man and 9 women; age range, 36 to 76 years), as summarized in Table 1. HTLV-1 seropositivity was examined using the particle agglutination methods (New Seroclit-anti-HTLV-1; Sanko; Tokyo, Japan). All patients were evaluated to be in a carrier stage. Seven of the patients had chronic bronchiolitis, one patient had hypersensitivity pneumonitis diagnosed by surgical biopsy, and two patients had

Characteristics of BALF Cells

Table 3 summarizes the results BALF cell analysis in HTLV-1–infected patients and healthy control subjects. Neither leukemic cells nor pathogens associated with opportunistic infection were found in BALF of these patients. In HTLV-1–infected patients, the mean total cell count was 5.7 × 105/mL (range, 0.8 to 12.7 × 105/mL) and lymphocyte proportion was 23.4% (range, 0.6 to 53.9%; > 20% in four patients). The proportion of neutrophils ranged from 0 to 59.5%, with a mean value of 17.0%. It should

Discussion

Clinical and epidemiologic studies789101112 have established that HTLV-1 is closely associated with certain bronchopulmonary disorders. Accumulation of lymphocytes and activated T cells, as well as abundant HTLV-1–infected T cells and viral activity, have been demonstrated in BALF of HTLV-1–infected patients.891011121314151625 Although HTLV-1 was suggested to be involved in bronchopulmonary lesions, characterized by lymphocytic accumulation, the precise mechanism of such response is not fully

ACKNOWLEDGMENT

The authors thank Dr. F. G. Issa (Word-Medex; Sydney, Australia) for reading and editing the manuscript.

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