PMID- 11683964
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190513
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 104
IP  - 2
DP  - 2001 Oct
TI  - Topical tacrolimus and cyclosporin A differentially inhibit early and late 
      effector phases of cutaneous delayed-type and immunoglobulin E hypersensitivity.
PG  - 235-42
AB  - Systemic and topical administration routes of tacrolimus and cyclosporin A (CsA) 
      were compared in effects on early and late phases of elicited T-cell-mediated 
      contact sensitivity (CS), and effects on early and late phases of cutaneous 
      immunoglobulin E (IgE) antibody-mediated hypersensitivity responses in mice. 
      Thus, both CS and IgE responses in the skin have an early mast-cell-dependent 
      phase, and also a late inflammatory phase. We measured the effects of both 
      immunosuppressants on both phases of the respective T cell versus IgE responses. 
      Systemic administration of both agents completely suppressed CS and IgE 
      late-phase responses, but failed to affect either early phase. In contrast, when 
      topical CsA was used, low doses abolished the early phase of IgE responses, but 
      even high doses did not inhibit the early phase of CS. Conversely, topical 
      tacrolimus inhibited the early phase of CS more potently than the early phase of 
      cutaneous IgE hypersensitivity responses. Thus, topical treatment was needed to 
      inhibit the early phases and the two agents acted differentially, suggesting 
      differing susceptibility of the early phases, that are probably due to different 
      signalling mechanisms. These studies underscore the potential value of topical 
      administration of these powerful immunosuppressive agents in the treatment of 
      allergic diseases that exhibit features of early-phase mast-cell-dependent 
      inflammation, and late inflammation due to mast cells or to T cells, such as 
      atopic dermatitis or asthma, since the early phase is predominantly susceptible 
      to topical application, while the last phase of both IgE and T-cell inflammation 
      responds to systemic treatment with both agents.
FAU - Geba, G P
AU  - Geba GP
AD  - Department of Internal Medicine, Yale University School of Medicine, New Haven, 
      CT 06520-8057, USA.
FAU - Ptak, W
AU  - Ptak W
FAU - Askenase, P W
AU  - Askenase PW
LA  - eng
GR  - P50 HL056389/HL/NHLBI NIH HHS/United States
GR  - P01 HL056389/HL/NHLBI NIH HHS/United States
GR  - AI-43371/AI/NIAID NIH HHS/United States
GR  - P30 AR041942/AR/NIAMS NIH HHS/United States
GR  - HL-56389/HL/NHLBI NIH HHS/United States
GR  - AR-41942/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Immunosuppressive Agents)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - Z4ZG7O5SZ9 (Picryl Chloride)
SB  - IM
MH  - Administration, Cutaneous
MH  - Animals
MH  - Cyclosporine/*therapeutic use
MH  - Dermatitis, Allergic Contact/immunology/*prevention & control
MH  - Dermatitis, Atopic/immunology/*prevention & control
MH  - Female
MH  - Immunoglobulin E/biosynthesis/immunology
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred CBA
MH  - Picryl Chloride/immunology
MH  - T-Lymphocytes/immunology
MH  - Tacrolimus/*therapeutic use
PMC - PMC1783292
EDAT- 2001/10/31 10:00
MHDA- 2002/01/05 10:01
PMCR- 2002/10/01
CRDT- 2001/10/31 10:00
PHST- 2001/10/31 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/31 10:00 [entrez]
PHST- 2002/10/01 00:00 [pmc-release]
AID - 1288 [pii]
AID - 10.1046/j.1365-2567.2001.01288.x [doi]
PST - ppublish
SO  - Immunology. 2001 Oct;104(2):235-42. doi: 10.1046/j.1365-2567.2001.01288.x.