PMID- 10586942
OWN - NLM
STAT- MEDLINE
DCOM- 19991209
LR  - 20131121
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 40
IP  - 13
DP  - 1999 Dec
TI  - Changes in cytokine mRNA levels in experimental corneal allografts after local 
      clodronate-liposome treatment.
PG  - 3194-201
AB  - PURPOSE: Corneal allograft rejection in rats can be prevented by subconjunctival 
      injections of liposomes containing dichloromethylene diphosphonate 
      (clodronate-LIP), which selectively eliminate macrophages. In this study, the 
      effect of clodronate-LIP treatment on cytokine mRNA levels in corneal allografts 
      was examined. METHODS: AO rats received corneal grafts of PVG rats. Rats were 
      either not treated or injected subconjunctivally with clodronate-LIP on the day 
      of transplantation and on postoperative days (PODs) 2, 4, 6, and 8. RNA was 
      isolated from the graft and rim of corneas at different times after 
      transplantation and from normal controls. Interleukin (IL)-1beta, IL-1 receptor 
      antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-12p40, tumor necrosis factor 
      (TNF)-alpha, TNF-beta/lymphotoxin (LT), interferon (IFN)-gamma, monocyte 
      chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 2 (MIP-2) mRNA 
      levels were analyzed by semiquantitative reverse transcription-polymerase chain 
      reaction (RT-PCR). RESULTS: Corneal rejection, observed in all untreated rats by 
      POD 12, was associated with increased mRNA levels of all cytokines investigated 
      in grafts and rims. Clodronate-LIP treatment prevented allograft rejection and 
      strongly decreased the levels of IL-1beta, IL-1RA, IL-2, IL-4, IL-6, IL-10, 
      IFN-gamma, TNF-beta/LT, MCP-1, and MIP-2 mRNA in grafts and IL-1 beta, IL-2, 
      IL-4, IL-6, and IFN-gamma mRNA in rims. Interleukin-12p40 mRNA levels were 
      unaltered in clodronate-treated rats, except for a transient increase in grafts 
      at POD 3. TNF-alpha mRNA levels were increased by clodronate-LIP in grafts and 
      rims early after transplantation (PODs 3 and 7). Despite a normal appearance, 
      long-term accepted corneal grafts (POD 100) contained mRNA for IL-10, IL-12p40, 
      TNF-alpha, MCP-1, and MIP-2. CONCLUSIONS: Clodronate-liposome treatment markedly 
      altered the mRNA levels of all cytokines investigated in corneal allografts. 
      These results may explain in part the mechanism by which clodronate-LIP treatment 
      prevents corneal allograft rejection.
FAU - Torres, P F
AU  - Torres PF
AD  - Department of Ophthalmology, Hospital Geral de Santo Antonio, Porto, Portugal.
FAU - Slegers, T P
AU  - Slegers TP
FAU - Peek, R
AU  - Peek R
FAU - van Rooijen, N
AU  - van Rooijen N
FAU - van der Gaag, R
AU  - van der Gaag R
FAU - Kijlstra, A
AU  - Kijlstra A
FAU - de Vos, A F
AU  - de Vos AF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Cytokines)
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 0 (Monokines)
RN  - 0 (RNA, Messenger)
RN  - 0813BZ6866 (Clodronic Acid)
SB  - IM
MH  - Animals
MH  - Blotting, Southern
MH  - Chemokine CCL2/genetics
MH  - Chemokine CXCL2
MH  - Clodronic Acid/*administration & dosage
MH  - Cornea/*drug effects/metabolism
MH  - *Corneal Transplantation
MH  - Cytokines/*genetics/metabolism
MH  - Drug Carriers
MH  - Graft Rejection/metabolism/*prevention & control
MH  - Graft Survival
MH  - Liposomes
MH  - Monokines/genetics
MH  - RNA, Messenger/*metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transplantation, Homologous
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1999 Dec;40(13):3194-201.