Influence of human T lymphotrophic virus type I on cryptogenic fibrosing alveolitis - HTLV-I associated fibrosing alveolitis: proposal of a new clinical entity

Abstract

Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4+ lymphocytes and is thought to modify their function; a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on cryptogenic fibrosing alveolitis (CFA), a chronic inflammatory interstitial lung disease of unknown aetiology. In order to clarify the influence of HTLV-I infection on CFA, 72 CFA patients with and without HTLV-I infection were examined. HTLV-I positive CFA patients were likely to have larger affected areas and to show traction bronchiectasis with honeycombing change. An imbalance of matrix metalloproteinases and tissue inhibitor of metalloproteinases were also observed in the BALF of HTLV-I positive CFA patients. CD3+/CD25+ lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients compared to negative patients. MIP-1alpha, IP-10 and sICAM 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-1alpha and IP-10 levels showed a significant positive correlation with percentage of CD3+/CD25 lymphocytes. HTLV-I positive CFA patients showed a larger lesion than negative patients and exhibited increased levels of certain cytokines that correlated with activated T cells in the BALF. We suggest that HTLV-I infection may contribute to the development of CFA via activation of T cells. We also propose that these features should be taken into consideration in the treatment of CFA in HTLV-I infected individuals.

Fig. 1

Comparison of cytokine levels in BALF between HTLV-I positive and negative CFA patients. The levels of MIP-1α, IP-10 and sICAM were significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different between two groups. Bar shows mean value in each group. (*P < 0·01, **P < 0·05, Mann–Whitney test).

Fig. 2

Correlation between percentage of CD3⁺/CD25⁺ lymphocytes and cytokine levels in BALF of HTLV-I positive CFA patients. The levels of MIP-1α, IP-10 and sICAM showed significant positive correlations with the percentage of CD3⁺/CD25⁺ lymphocytes. VS also showed significant positive correlations with the percentage of CD3⁺/CD25⁺ lymphocytes.