PMID- 7930875
OWN - NLM
STAT- MEDLINE
DCOM- 19941107
LR  - 20131121
IS  - 0022-2143 (Print)
IS  - 0022-2143 (Linking)
VI  - 124
IP  - 4
DP  - 1994 Oct
TI  - Modulation of glomerular structure and function in murine lupus nephritis by 
      methylprednisolone and cyclophosphamide.
PG  - 496-506
AB  - The effects of methylprednisolone and cyclophosphamide were examined in a murine 
      model of lupus nephritis (MRL-1pr/1pr). Animals were assigned to four groups at 
      12 weeks of age. Mice in the control group received intraperitoneal saline 
      solution either daily or weekly. Animals in the low-dose methylprednisolone 
      (MPLD) group received 6 mg/kg/day intraperitoneal methylprednisolone; those in 
      the high-dose methylprednisolone (MPHD) group received 12 mg/kg/day 
      intraperitoneal methylprednisolone. Animals in the cyclophosphamide group 
      received 50 mg/kg/wk intraperitoneal cyclophosphamide. Animals surviving to 24 
      weeks were examined. MPHD and cyclophosphamide treatments were associated with 
      maintenance of normal glomerular filtration rates and the development of only 
      minimal proteinuria. However, detailed morphometric evaluation of the glomerulus 
      revealed glomerular enlargement and mesangial matrix expansion in both groups. 
      Unlike MPHD-treated mice, cyclophosphamide-treated animals demonstrated a marked 
      reduction in the number of osmophilic dense deposits along the glomerular 
      capillary walls. MPLD had little effect on function, despite significant 
      reductions in cell proliferation and anti-double-strand DNA antibodies. Tumor 
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were 
      dramatically increased in plasma of control animals. Treatment with 
      methylprednisolone and cyclophosphamide dramatically reduced TNF-alpha but not 
      IL-6. Treatment also reduced renal IL-1 beta, TNF-alpha and transforming growth 
      factor-beta mRNA levels compared with untreated mice. Despite minimal serologic 
      activity and preservation of renal function, neither cyclophosphamide nor 
      methylprednisolone was able to completely suppress disease activity, as measured 
      by increased cytokine production and glomerular structural injury. The inability 
      of treatment to reduce IL-6 levels may explain the resistance to treatment in 
      this model.
FAU - Kiberd, B A
AU  - Kiberd BA
AD  - Department of Medicine, Queen's University, Kingston, Ontario, Canada.
FAU - Young, I D
AU  - Young ID
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lab Clin Med
JT  - The Journal of laboratory and clinical medicine
JID - 0375375
RN  - 0 (Interleukin-6)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - X4W7ZR7023 (Methylprednisolone)
SB  - IM
CIN - J Lab Clin Med. 1994 Oct;124(4):470-2. PMID: 7930870
MH  - Animals
MH  - Base Sequence
MH  - Cyclophosphamide/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Glomerular Filtration Rate
MH  - Interleukin-6/metabolism
MH  - Kidney Glomerulus/pathology/physiopathology
MH  - Lupus Nephritis/drug therapy/metabolism/*pathology/*physiopathology
MH  - Methylprednisolone/*pharmacology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Molecular Sequence Data
MH  - Oligonucleotide Probes/genetics
MH  - Polymerase Chain Reaction
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1994/10/01 00:00
MHDA- 1994/10/01 00:01
CRDT- 1994/10/01 00:00
PHST- 1994/10/01 00:00 [pubmed]
PHST- 1994/10/01 00:01 [medline]
PHST- 1994/10/01 00:00 [entrez]
AID - 0022-2143(94)90062-0 [pii]
PST - ppublish
SO  - J Lab Clin Med. 1994 Oct;124(4):496-506.