PMID- 1757474
OWN - NLM
STAT- MEDLINE
DCOM- 19920204
LR  - 20081121
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 46
IP  - 4
DP  - 1991 Aug
TI  - Cytokine induction in HTLV-I associated myelopathy and adult T-cell leukemia: 
      alternate molecular mechanisms underlying retroviral pathogenesis.
PG  - 302-11
AB  - 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 gamma-interferon 
      (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 
      beta), and transforming growth factor-beta 1 (TGF-beta 1) in the peripheral blood 
      of HAM/TSP and ATL patients as well as asymptomatic seropositive carriers. 
      IFN-gamma, TNF-alpha, and IL-1 beta 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-beta 1 mRNA than HAM/TSP and seropositive carriers. In addition, 
      TNF-alpha and IL-1 beta 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-beta 1 protein into the culture 
      medium than T-cells derived from HAM/TSP patients. Collectively these results 
      suggest that induction of IFN-gamma, TNF-alpha, and IL-1 beta 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-alpha and IL-1 beta 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-beta 
      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.
FAU - Tendler, C L
AU  - Tendler CL
AD  - Metabolism Branch, National Cancer Institute, National Institutes of Health, 
      Bethesda, Maryland 20892.
FAU - Greenberg, S J
AU  - Greenberg SJ
FAU - Burton, J D
AU  - Burton JD
FAU - Danielpour, D
AU  - Danielpour D
FAU - Kim, S J
AU  - Kim SJ
FAU - Blattner, W A
AU  - Blattner WA
FAU - Manns, A
AU  - Manns A
FAU - Waldmann, T A
AU  - Waldmann TA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Cytokines)
RN  - 0 (DNA, Single-Stranded)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Base Sequence
MH  - Central Nervous System/pathology
MH  - Cytokines/*metabolism
MH  - DNA, Single-Stranded
MH  - Female
MH  - *Gene Expression Regulation, Viral
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-1/metabolism
MH  - Leukemia, T-Cell/complications/*immunology
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Paraparesis, Tropical Spastic/*immunology
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis
MH  - Retroviridae/*pathogenicity
MH  - T-Lymphocytes/immunology
MH  - Transforming Growth Factor beta/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation
EDAT- 1991/08/01 00:00
MHDA- 1991/08/01 00:01
CRDT- 1991/08/01 00:00
PHST- 1991/08/01 00:00 [pubmed]
PHST- 1991/08/01 00:01 [medline]
PHST- 1991/08/01 00:00 [entrez]
AID - 10.1002/jcb.240460405 [doi]
PST - ppublish
SO  - J Cell Biochem. 1991 Aug;46(4):302-11. doi: 10.1002/jcb.240460405.