PMID- 8707444
OWN - NLM
STAT- MEDLINE
DCOM- 19960911
LR  - 20190909
IS  - 0192-0561 (Print)
IS  - 0192-0561 (Linking)
VI  - 17
IP  - 10
DP  - 1995 Oct
TI  - The specific type IV phosphodiesterase inhibitor rolipram combined with adenosine 
      reduces tumor necrosis factor-alpha-primed neutrophil oxidative activity.
PG  - 793-803
AB  - Monocytes and macrophages produce tumor necrosis factor-alpha (TNF alpha) in 
      response to microbial products including endotoxin. TNF alpha is a potent primer 
      of neutrophil (PMN) oxidative activity. Certain xanthine phosphodiesterase (PDE) 
      inhibitors such as pentoxifylline have been shown to inhibit stimulated oxidative 
      activity in PMN. In the present study, the non-xanthine PDE type IV inhibitor 
      rolipram (4-[3'-cyclopentyloxy-4'-methoxyphenyl]-2-pyrrolidone) alone and in 
      combination with adenosine is examined as a potential modulator of TNF 
      alpha-primed PMN oxidative activity. Attainable in vivo concentrations of 
      rolipram and physiological concentrations of adenosine alone and together 
      synergistically decreased rhTNF alpha-primed suspended PMN oxidative activity 
      stimulated by the chemoattractant f-met-leu-phe. The rolipram effect was 
      reversible by washing, and rolipram had a comparable effect if added before or 
      after priming, indicating that its effect was on the primed response rather than 
      on priming per se. In addition, rolipram especially when combined with adenosine, 
      decreased rhTNF alpha-stimulated PMN adherence to a fibrinogen-coated surface, 
      and the oxidative burst of rhTNF alpha-stimulated adherent PMN. The specific 
      adenosine A2a receptor agonists CGS 21680 and WRC-0474 had comparable activity to 
      adenosine in these experiments. Adenosine (or CGS 21680) combined with rolipram 
      synergistically increased f-met-leu-phe-stimulated PMN cAMP content. The effects 
      of both adenosine and rolipram with adenosine could be only partly counteracted 
      by treatment of the PMN with the protein kinase A inhibitor KT 5720, indicating 
      that protein phosphorylation is only partially involved. Rolipram activity was 
      about 1000 x (by molar concentration) greater than pentoxifylline in comparable 
      assays. Thus, rolipram, especially when combined with adenosine, has potent 
      modulating effects on PMN activation and may be useful in decreasing inflammatory 
      tissue damage in patients with sepsis.
FAU - Sullivan, G W
AU  - Sullivan GW
AD  - Department of Medicine, University of Virginia, Charlottesville 22908, USA.
FAU - Carper, H T
AU  - Carper HT
FAU - Mandell, G L
AU  - Mandell GL
LA  - eng
GR  - R01AI09504/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Int J Immunopharmacol
JT  - International journal of immunopharmacology
JID - 7904799
RN  - 0 (Carbazoles)
RN  - 0 (Indoles)
RN  - 0 (Phenethylamines)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11062-77-4 (Superoxides)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - 58HV29I28S (KT 5720)
RN  - K676NL63N7 (Rolipram)
RN  - K72T3FS567 (Adenosine)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Adenosine/analogs & derivatives/*pharmacology
MH  - *Carbazoles
MH  - Drug Synergism
MH  - Humans
MH  - In Vitro Techniques
MH  - Indoles/pharmacology
MH  - Neutrophils/*drug effects
MH  - Pentoxifylline/pharmacology
MH  - Phenethylamines/pharmacology
MH  - Phosphodiesterase Inhibitors/*pharmacology
MH  - Pyrroles/pharmacology
MH  - Pyrrolidinones/*pharmacology
MH  - Respiratory Burst/drug effects
MH  - Rolipram
MH  - Superoxides/metabolism
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - 019205619500073B [pii]
AID - 10.1016/0192-0561(95)00073-b [doi]
PST - ppublish
SO  - Int J Immunopharmacol. 1995 Oct;17(10):793-803. doi: 
      10.1016/0192-0561(95)00073-b.