PMID- 8752839
OWN - NLM
STAT- MEDLINE
DCOM- 19961213
LR  - 20210409
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 107
IP  - 1
DP  - 1996 Jul
TI  - Type 4 phosphodiesterase inhibitors have clinical and in vitro anti-inflammatory 
      effects in atopic dermatitis.
PG  - 51-6
AB  - Increased cyclic AMP-phosphodiesterase activity in peripheral blood leukocytes is 
      associated with the immune and inflammatory hyperreactivity that characterizes 
      atopic dermatitis. Atopic phosphodiesterase has high sensitivity to a variety of 
      enzyme inhibitors, suggesting an increased therapeutic advantage. The objective 
      of this study was to use in vitro assays to identify a potent phosphodiesterase 
      inhibitor and then to investigate its effectiveness in treating atopic 
      dermatitis. Leukocyte enzyme activity was measured by radioenzyme assay, whereas 
      prostaglandin E2 and interleukins 10 (IL-10) and 4 (IL-4) were measured in 24-h 
      culture supernatants of mononuclear leukocytes by immunoassays. The effect of a 
      topical phosphodiesterase inhibitor on atopic dermatitis lesional skin was 
      assessed by double-blind, paired comparisons of active drug and placebo ointments 
      applied to symmetrically involved sites over a 28-d period. Using in vitro, 
      assays, we demonstrated the ability of selective high-potency phosphodiesterase 
      inhibitors to reduce prostaglandin E2, IL-10, and IL-4 production in atopic 
      mononuclear leukocyte cultures. We selected the Type 4 phosphodiesterase 
      inhibitor, CP80,633, based on its inhibitory potency, for clinical testing by 
      topical, bilateral paired comparisons in 20 patients with atopic dermatitis and 
      demonstrated significant reductions of all inflammatory parameters. 
      Phosphodiesterase inhibitors modulate several pathways contributing to the 
      exaggerated immune and inflammatory responses, which characterize atopic 
      dermatitis. This in vivo demonstration of anti-inflammatory efficacy may provide 
      a useful alternative to the over-reliance on corticosteroid therapy in atopic 
      disease.
FAU - Hanifin, J M
AU  - Hanifin JM
AD  - Oregon Health Sciences University, Department of Dermatology, Portland 
      97201-3098, USA.
FAU - Chan, S C
AU  - Chan SC
FAU - Cheng, J B
AU  - Cheng JB
FAU - Tofte, S J
AU  - Tofte SJ
FAU - Henderson, W R Jr
AU  - Henderson WR Jr
FAU - Kirby, D S
AU  - Kirby DS
FAU - Weiner, E S
AU  - Weiner ES
LA  - eng
GR  - AI18615/AI/NIAID NIH HHS/United States
GR  - AI34578/AI/NIAID NIH HHS/United States
GR  - AI7758/AI/NIAID NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Administration, Topical
MH  - Adult
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Dermatitis, Atopic/blood/*drug therapy
MH  - Dinoprostone/antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Interleukin-10/antagonists & inhibitors
MH  - Interleukin-4/antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Monocytes/metabolism
MH  - Phosphodiesterase Inhibitors/classification/*therapeutic use
EDAT- 1996/07/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
AID - S0022-202X(15)42624-7 [pii]
AID - 10.1111/1523-1747.ep12297888 [doi]
PST - ppublish
SO  - J Invest Dermatol. 1996 Jul;107(1):51-6. doi: 10.1111/1523-1747.ep12297888.