PMID- 1902846
OWN - NLM
STAT- MEDLINE
DCOM- 19910613
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 72
IP  - 6
DP  - 1991 Jun
TI  - Effects of recombinant human interleukin-2 and tumor necrosis factor-alpha with 
      or without interferon-gamma on human thyroid tissues from patients with Graves' 
      disease and from normal subjects xenografted into nude mice.
PG  - 1296-301
AB  - We have compared the effects of interleukin-2 (IL-2) or tumor necrosis 
      factor-alpha (TNF alpha) administration with or without interferon-gamma (IFN 
      gamma) on Graves' and normal thyroid tissue xenografts in the nude mouse (in the 
      absence of an intact immune system) in terms of possible functional, 
      immunological, or histological changes. The dosages of recombinant human IL-2, 
      TNF alpha, and IFN gamma given to each mouse were 250, 800, and 4000 U, 
      respectively; they were injected ip daily for 6 consecutive weeks. The parameters 
      measured included the free T4 index, thyroid autoantibodies, and mouse TSH during 
      the course of the study. Thyroid epithelial cell (TEC) HLA-DR expression was 
      measured in thyroid tissue before xenotransplantation and at death; in addition, 
      light microscopic studies were carried out at those times. There were no 
      significant differences in thyroid function between the results in unstimulated 
      (control) animals and those obtained with cytokine administration in either group 
      of tissues, with the exception of the group receiving TNF alpha together with IFN 
      gamma; in this latter group, the free T4 index declined significantly 4-6 weeks 
      after commencement of treatment in the animals with normal thyroid tissue 
      xenografts. The reduction of thyroid function induced by the combination of IFN 
      gamma and TNF alpha observed in normal thyroid tissue may be due to inhibition of 
      thyroperoxidase and thyroglobulin gene transcription. However, there was no such 
      effect on the Graves' thyroid tissue xenografts, perhaps because of 
      down-regulation of this tissue in response to cytokines, after having been 
      released from long term in vivo immune stimulation. On the other hand, TNF alpha 
      plus IFN gamma induced TEC HLA-DR expression on both types of thyroid xenografts 
      at death, although IL-2 alone did not induce HLA-DR expression, and IFN gamma 
      induced TEC significantly only on normal thyroid xenografts (but not on Graves' 
      xenografts). In light microscopic examination, Graves' thyroid xenografts treated 
      with IL-2 alone or TNF alpha plus IFN gamma appeared normal at death. In 
      addition, normal thyroid xenografts treated with the same cytokines did not show 
      discernible differences compared to those at human surgery or when the xenografts 
      were untreated at death. We conclude that Graves' TEC did not differ from normal 
      TEC in any significant fashion at the time of death, aside from a reduced 
      responsiveness to the stimuli applied.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Kasuga, Y
AU  - Kasuga Y
AD  - Endocrinology Research Laboratory, Wellesley Hospital, University of Toronto, 
      Ontario, Canada.
FAU - Matsubayashi, S
AU  - Matsubayashi S
FAU - Akasu, F
AU  - Akasu F
FAU - Miller, N
AU  - Miller N
FAU - Jamieson, C
AU  - Jamieson C
FAU - Volpe, R
AU  - Volpe R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Interleukin-2)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9002-71-5 (Thyrotropin)
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - Animals
MH  - Epithelium/immunology/pathology
MH  - Graves Disease/immunology/pathology/*physiopathology
MH  - HLA-DR Antigens/analysis
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-2/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Recombinant Proteins
MH  - Reference Values
MH  - Thyroid Gland/drug effects/physiopathology/*transplantation
MH  - Thyrotropin/blood
MH  - Thyroxine/blood
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1991/06/01 00:00
MHDA- 1991/06/01 00:01
CRDT- 1991/06/01 00:00
PHST- 1991/06/01 00:00 [pubmed]
PHST- 1991/06/01 00:01 [medline]
PHST- 1991/06/01 00:00 [entrez]
AID - 10.1210/jcem-72-6-1296 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1991 Jun;72(6):1296-301. doi: 10.1210/jcem-72-6-1296.