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Cytokine induction in HTLV‐I associated myelopathy and adult T‐cell leukemia: Alternate molecular mechanisms underlying retroviral pathogenesis
Author(s) -
Tendler Craig L.,
Greenberg Steven J.,
Burton Jack D.,
Danielpour David,
Kim SeongJin,
Blattner William A.,
Manns Angela,
Waldmann Thomas A.
Publication year - 1991
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240460405
Subject(s) - tropical spastic paraparesis , immunology , cytokine , tumor necrosis factor alpha , t cell leukemia , human t lymphotropic virus 1 , biology , leukemia , pathogenesis , virology , medicine , myelopathy , neuroscience , spinal cord
The human T‐cell lymphotropic virus type I (HTLV‐I) is capable of inducing a variety of host cellular genes including many of the cytokines responsible for immune regulation and osteoclast activation. This derangement in cytokine expression may contribute to the panoply of disease states associated with HTLV‐I infection such as the adult T‐cell leukemia (ATL) and HTLV‐I associated myelopathy/tropical spastic paraparesis (HAM/TSP). We wished to determine if there was a correlation between the expression of an array of cytokines and the diverse clinical manifestations of ATL and HAM/TSP. Utilizing the techniques of specific mRNA amplification by the polymerase chain reaction (PCR) as well as Northern blotting, we analyzed the ex vivo mRNA expression of γ‐interferon (IFN‐γ), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and transforming growth factor‐β, (TGF‐β 1 ) in the peripheral blood of HAM/TSP and ATL patients as well as asymptomatic seropositive carriers. IFN‐γ, TNF‐α, and IL‐1β transcripts were up‐regulated in patients with HAM/TSP and seropositive carriers when compared to their levels in ATL and normal controls. In contrast, the ATL patients constitutively expressed higher levels of TGF‐α 1 mRNA than HAM/TSP and seropositive carriers. In addition, TNF‐α and IL‐1β serum levels were elevated in HAM/TSP, but not in ATL patients nor seropositive carriers. However, the circulating leukemic cells from ATL patients secreted increased levels of TGF‐β 1 protein into the culture medium than T‐cells derived from HAM/TSP patients. Collectively these results suggest that induction of IFN‐γ, TNF‐alpha;, and IL‐β in HAM/TSP may initiate an inflammatory cascade with subsequent events leading to immune mediated destruction of the central nervous system in these patients. Expression of osteoclast activators such as TNF‐α and IL‐β is not associated with hypercalcemia in ATL. Finally, impaired cellular and humoral immune responses present in ATL, but not in HAM/TSP, may be related to elevated levels of TGF‐β 1 produced by the leukemic cells. These differences in retroviral‐induced host cytokine expression in ATL and HAM/TSP suggest alternate roles in disease pathogenesis.