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Cetirizine inhibits TNFα-induced VCAM-1 expression and NF-κB activation in human endothelial cells in vitro
ESDR I JSID I SID Abstracts
1249
1252
A NOVEL DOSING REGIME OF CYCLOSPOm A IN SEVERE ATOPIC DERMATITIS W Czech. Vdlmnen. E. Schaof. Umventtv of Fraburs; M Brautwm. G. Welduuzcr, Nova& Phamm GmbH. Nbmherr. Germanv In tbls multicenter, double-blind study 106 patmtts wtb severe atopic dermautis were randomly allocated to a treatment wth dmly doses of e&r I.50 or 300 mg cyclospam A micrcemulsmn (Neoral) After two weeks of treatment the dose could he reduced by 50% m responders wrtb a reductmn of at Icast 50% m the Total-Body-SeventyAssessment (TBSA) score The TBSA score was decreased from 59 0 to 39 3 m the 150 mg-group and from 60.7 to 33 2 m the 300 mg-group at week 2 (p < 0 05) Altba@ only dose reductions were allowed bv the orotocol the TBSA score showed a futtber decrease in the following EIX w&ks m both groups The total nmprovement was 45 6% and 56 5% m the groups with the lower and the higher stmtmg dose. respectively @ = n s ) Simdar improvements were observed for the affected area and for more SubJectwe parameters, bke pmntus and sleep dwterbances Three of 53 pabents from the 300 mg-Sreup discontinued the study because of side effects (gastromtcstinal complaints, headache, gmSwa, hyperplasw effluvium and parestixw). No paoent discontmued due to adverse events m the 150 mg-group ‘Ihere were only small maeases m serum creatinine amounting to about 1% m the 150 mg-group and 6% m the 300 mg-group @ = 0.0002) The effects on dlseasc actwty and renal timctmn were not dependent on body weight From the results of thrs study it can bc concluded that tbc low start dose of IS0 mg was somewhat less effective but better tolerated than 300 mg and that body we& mdependent doses of Neoral are clearly effbchve and safe m atopic dermatitis
ACQUISTION OF A SLOW ACFP(LATOR PHENOTYPEIN AIDS PATIENTS WlTH A RAPID ACEIYLATOR GENOTYPE: AN EXPLANATION FOR HlGH FREQUENCY OF CUTANEOUS SULFONAMIDES REACTIONS IN AIDS H)PULATION?. Pierre Wolkemteinl. Francoise Baud-Camus2. Svlvaine Lecwur3, Jean-Domirdaue Poveda4. Roben. Fain”&. Philiooe Beaune3. Mutiel Eliaszewicz~. Qlivicr Cb”sid”w6 for the m. IDepartment of Dermatology, CHU HaniMondor, Cr.&l; *INSERM U 75, CHU Necker, tis; 3tkpaiment of Virology, Instihlt Pasteur, Paris. Sulfonamide-induced reactions has been linked with a slow acetylation. I” AIDS patients. an unexpected high rate of slow acetylator phenotype has been found. We demonsbated the acquisition of a slow acetylator phenotype in AIDS patients with a rapid acetylator genotype during acute illnesses. 15 AIDS patients hospitalized for pneumocystosis or toxoplasmosis were evaluated for acetylation expression. Patients DNA was tested for the detection of N-acetyltransferase2 mutations Ml, M2, M3, M4 (slow acetylator genotype = 2 mutations; rapid acetylator genotype = no or only one mutation). After admission, patients were given caffeine (200 mg). Urine samples were collected 4 hours later. Urinary concentntions of AAMU, and IX were measured. The ratio AAMU/IX was used to assess the acetvlator ohenotvoe (.ratio < I.8 = slow phenotype ; ratio 21.8 = rapid phenotype). i patie;ts had*; s&v acetylator genotype, IO a rapid acetylator genotype.9 had a slow acetylator phenotype, and 6 a rapid acetylator phe&xype.~ patie& with a rapid acet$ator genotype expressed a-slow acetylator phenotype. Acute illnesses in AIDS patients can modify the expression of a rapid acetylamr genotype into a slow acetylator phenotype.This modification of acetylation expression could explain the high rate of cutaoeou.ssulfonamides adverse drug reactions in this population.
1250
1253
MOUSE AND HUMAN SKIN BY TOPICAL IMMUNERESPONSEMODIFIER,IMIQUIMOD.RL Mdler, MA Tomm, I Am&S& a, DJ McDermott,SL Pamsh, MH Smith and BB Slade. 3M Pharmaceuticals,St Paul,
TACROLIMUS OINTMENT (TO) FOR ADULTS WITH MODERATE TO SEVER!? ATOPIC DERMATITIS (AD): A DOSE ESCALATION STUDY. S. Kang and the Tacrolimus Ointment Study Group, University ofMichigan, AM Arbor, MI A multicenter, randomized, double-blind, vehicle-controlled(V), sequential group, dose escalation study was designed to evaluate the safety and efficacy of 0.03%, 0. I%, 0.3% TO in adults with moderate to severe AD tiecting at least 76% of their total body surface area (BSA). Patients (n=26) applied study drug BID for a maximum of 3 weeks No patients in the V or 0.03% groups versus 100% in patients in the 0.1% and 86% in pat&s in the 0.3% groups had marked or excellent improvement at the end of treatment (BOT). Five patients (84%) in the V group discontinued the study due to lack ofefficacy. Application of any of the three TO concentrations resulted in a greater reduction in &&ted BSA than observed with V; mean changes from baseline in BSA a&ted were: V -5; 0.03% -25; 0.1% -40; and 0.3% -53 Individual signs and symptoms of AD remained the same or worsened in the V group while improvement was observed in all patients applying TO. All three TO groups showed a decrease in a mean composite score by Day 4 which was maintained throw& _ EOT; in contrast. this score increased (worsened1 ii the-Vgroup; at EOT, mean changes from baseline in composite scores were: V group +2; 0.03% -4,O. 1% -7; and 0.3% -8. Application site adverse events (AE) were reported for 50% oftbose administered either V or TO,most ofthese AE had their onset within the first 4-5 days of treatment and subsided by Day 8. Skin burning, folliculitis and pturitus were the most common application AE Nine patients bad B peak tacrolimus blood concentration LI ng/mL. No apparent relationship between blood concentration and AE was observed. No significant changes in laboratory profile were see”. TO showed therapeutic benefit and was safe when repeatedly applied over a large portion ofthe BSA.
CYTOKINE INDUCTION IN HAIRLESS
MN and 1Umv. TexasMedicalBranch,Galveston,TX.
Imiqunnodcream 5% has recentlybecome avatlable m the US for the keeatment of external gemtal and penanal warts caused by human papdlomavirus (HPT9. One OhJective of these studms was to determme cytokine induchon followmg topwal lmlqmmcd applicahon to hanless m,ce and ma Phase I vehicle controlled study, to human gemtal wertpahents A second obJcctive of the human study was to measure effects of drug treatment on cell makers and on HPV DNA and IIPV gene expressmn m IIPV pahents. In the mouse study, bmpsies were take,, at the treatment s,te and from the other side of the mmne at the time of drug apphcatmn, at I hour and at 2 hours. In humans. hiopsles of the wart treatment site were taken at drug mihatmn, at 6 weeks and at the end of I6 weeks treatment or wart clearance. Human bmpstes were analyzed by reverse transcriptase (RT) polymerase cham reactm” (PCR) for mRNA for several cytokines, cell markers and WV genes and by PCR for IIPV DNA (copxs/cell). Moue bmpsies were analyzed for interferon alpha (EWa) and TN&a “RNA by RT-PCR and for cytokme protem levels. In mice, increases were seen m “RNA for IF&? and for IFN and TN&a protein at the treatment site but not in bmpsxs from the untreated side of the mice. In humans, nniquimod treahnent caused increases in mRNA for IPN-a, TNFa. EN-P, IF’N-7, and IL-lZp40. Since mRNA for the IFN inducible protein, Z’S’oligadenylate synthetase was Increased, we also conclude that IFN-a protem was mcreased. T-cell marker CD4 mRNA was also mcreased HPV DNA load and mRNA for HPV L I protem were slgniiicantly decreased and wart we was decreased m all patients treated wth tmlqmmcd m tlus study. These results m&c& that topical imlqmmod is an effectwe local cytokme inducer in skin and an effectne treatment for HPV lesmns m humans.
1251
1254
TREATMENT OF HIV-RELATED EOSINOPHILIC FOLLICULITIS WITH ITRACONAZOLE PRODUCES CLINICAL REMISSION AND NORMALIZATION OF PLASMA EOSINOPHILS AND IgE. Michael Maiors. Melanie Adams. Reoato Oration, Krista Sharp. Roger Wibon. Irene Dounhertv and Ponaisoo Crw Jr., Dept. of Dermatology, University of Texas Southwestern Med. Ctr, DaIIas, TX, USA. EosioophiIIc folllculitb (EF) is B markedly pnrItic disease of undetermined eticdogy that is highly prevalent in HIV+ individuaI8; eosbwphilin and high plasma IgE are assoeIatedfeatures. Itrsconazole and metronidazole hwe each been reported to be etlicacious treatments, although neither drug has been subjected to controlled study. Demodex mites have been causally Implicated, although the organism la insensitive to itrneonuole or metronidazole. To evaluate therapeutic &lacy, we conducted P prospective trial in which HIV+ patients who fulfilled strict clinical, histologic and laboratory criteria for EF (including culture of lesional skin negative for bacteria and fungi) were randomized to 3 peroral treahnents for 4 rks: itraconazok (ZOOmR BID), met~cmidszole (500 mg BID),.and an mti-mite agent, lvermectin (200 pg/wk). butcomes were evaluated in double-blinded fashion nt 0.2.4 and 8 wks. and analvzed using repeeted measurer of vsriance and the KruskaI-Wallace test. Itracon&Ie-treated patients had significantly reduced mean lesion counts and extent of &In involvement, Iasting at least 4 wka past treatment termination. This remission was paralleled by normnlization of ewinophllin and plasma IgE, and improvement in 4 of IO quality-of-life meswres (itching, mood, &In health, and productivity at work). By eontmst, metronidazole- or ivermectln-treated patients exhibited either no change or deterioration in these parameters. These studies represent the first controlIed, randomized and doubkblinded validation of the efticacy of itraeooazole In the treatment of HIV-related EF. Our findings indicate that itrsconazole exerts P beneficial immunologic effect separate from its known anti-fungal actIvIty.
CETIRIZINE ;F-zB ran
INHIBITS
AzT!VAT!ON Lou s
ette J an
TNFa-INDUCED
IN ,HUMAN
. JeawP~uxP.
VCAM-1 EN?OhTEELIAL
EXPRESSION CELLS IN
AND VITRO.
e . . me_ M, elMelac~ Pierre G ras*. Louis D”bettret* and Laurence Micbcl*. •INSE~~M ~312, Latmratoire & Dcrmamlogie, H*pital Saint-Louis. Pais;%CB Pharma S.A.. Nantme, Prance. Cetirizine is a potent HI-receptor antagonist that possesses
anti-inflammatory properties like modulation of eosinopbil infdhation in viva in cutaneous sites following allergenchallenge. Cetitizine has been shown to reduce the expression of intercellular adhesion molecule-l (ICAM-1) on conjonctivalepitbelial cells in viva after antigeoic stimulation. To better caracterize the mechanism of action of cetirizine on adhesion molecule expression, we investigated the in vim effect of cetirizine on cytokineinduced expression of vascular cell adhesion molecule-l (VCAM-I). E-selectin @LAM-I) and ICAM-I in cultured human umbilical vein endotbelial cells (HUVEC) using immunohistochemistry, cytofluorimetty and quantitative ELISA. The neahnent with cetbizine (10mt3Mto lOAM) had littleeffect on ICAM-I and ELAM-I expression. However, the expression of VCAM-I on HIJVBC stimolatedby either IO or 100 U/ml of TNFa during 16 hours was significantly reduced by cetirizine hzatmem according to a dose-dependent manner. TNFa-activation of VCAM-I tmnscription in endothclial cells depends on the activationof NF-rB-like transcriptional proteins. Therefore, we explored the mode of action of cetirizine on NF-xB activation using electrophoretc mobility shift assay (EMSA). Our results clearly demonstrated that, according to a dose-dependent manner. cetirizbx treatment inhibited the activation of NF-xB induced by IO U/ml of TNFa in HUVEC. Slmilarresults were obtained using human damal mJcrovascularendotbeIiaI cells. In conclusion. “or work demonstrates that cet&ioe modulates VCAM-I expression on vascularendotbelial cells by acting at the level of gene transcription. By inhibiting activationof the transcription factorNF-rB, cetirizine might regulate the proinflammatory response of endothelium within tissues.
1249
1252
A NOVEL DOSING REGIME OF CYCLOSPOm A IN SEVERE ATOPIC DERMATITIS W Czech. Vdlmnen. E. Schaof. Umventtv of Fraburs; M Brautwm. G. Welduuzcr, Nova& Phamm GmbH. Nbmherr. Germanv In tbls multicenter, double-blind study 106 patmtts wtb severe atopic dermautis were randomly allocated to a treatment wth dmly doses of e&r I.50 or 300 mg cyclospam A micrcemulsmn (Neoral) After two weeks of treatment the dose could he reduced by 50% m responders wrtb a reductmn of at Icast 50% m the Total-Body-SeventyAssessment (TBSA) score The TBSA score was decreased from 59 0 to 39 3 m the 150 mg-group and from 60.7 to 33 2 m the 300 mg-group at week 2 (p < 0 05) Altba@ only dose reductions were allowed bv the orotocol the TBSA score showed a futtber decrease in the following EIX w&ks m both groups The total nmprovement was 45 6% and 56 5% m the groups with the lower and the higher stmtmg dose. respectively @ = n s ) Simdar improvements were observed for the affected area and for more SubJectwe parameters, bke pmntus and sleep dwterbances Three of 53 pabents from the 300 mg-Sreup discontinued the study because of side effects (gastromtcstinal complaints, headache, gmSwa, hyperplasw effluvium and parestixw). No paoent discontmued due to adverse events m the 150 mg-group ‘Ihere were only small maeases m serum creatinine amounting to about 1% m the 150 mg-group and 6% m the 300 mg-group @ = 0.0002) The effects on dlseasc actwty and renal timctmn were not dependent on body weight From the results of thrs study it can bc concluded that tbc low start dose of IS0 mg was somewhat less effective but better tolerated than 300 mg and that body we& mdependent doses of Neoral are clearly effbchve and safe m atopic dermatitis
ACQUISTION OF A SLOW ACFP(LATOR PHENOTYPEIN AIDS PATIENTS WlTH A RAPID ACEIYLATOR GENOTYPE: AN EXPLANATION FOR HlGH FREQUENCY OF CUTANEOUS SULFONAMIDES REACTIONS IN AIDS H)PULATION?. Pierre Wolkemteinl. Francoise Baud-Camus2. Svlvaine Lecwur3, Jean-Domirdaue Poveda4. Roben. Fain”&. Philiooe Beaune3. Mutiel Eliaszewicz~. Qlivicr Cb”sid”w6 for the m. IDepartment of Dermatology, CHU HaniMondor, Cr.&l; *INSERM U 75, CHU Necker, tis; 3tkpaiment of Virology, Instihlt Pasteur, Paris. Sulfonamide-induced reactions has been linked with a slow acetylation. I” AIDS patients. an unexpected high rate of slow acetylator phenotype has been found. We demonsbated the acquisition of a slow acetylator phenotype in AIDS patients with a rapid acetylator genotype during acute illnesses. 15 AIDS patients hospitalized for pneumocystosis or toxoplasmosis were evaluated for acetylation expression. Patients DNA was tested for the detection of N-acetyltransferase2 mutations Ml, M2, M3, M4 (slow acetylator genotype = 2 mutations; rapid acetylator genotype = no or only one mutation). After admission, patients were given caffeine (200 mg). Urine samples were collected 4 hours later. Urinary concentntions of AAMU, and IX were measured. The ratio AAMU/IX was used to assess the acetvlator ohenotvoe (.ratio < I.8 = slow phenotype ; ratio 21.8 = rapid phenotype). i patie;ts had*; s&v acetylator genotype, IO a rapid acetylator genotype.9 had a slow acetylator phenotype, and 6 a rapid acetylator phe&xype.~ patie& with a rapid acet$ator genotype expressed a-slow acetylator phenotype. Acute illnesses in AIDS patients can modify the expression of a rapid acetylamr genotype into a slow acetylator phenotype.This modification of acetylation expression could explain the high rate of cutaoeou.ssulfonamides adverse drug reactions in this population.
1250
1253
MOUSE AND HUMAN SKIN BY TOPICAL IMMUNERESPONSEMODIFIER,IMIQUIMOD.RL Mdler, MA Tomm, I Am&S& a, DJ McDermott,SL Pamsh, MH Smith and BB Slade. 3M Pharmaceuticals,St Paul,
TACROLIMUS OINTMENT (TO) FOR ADULTS WITH MODERATE TO SEVER!? ATOPIC DERMATITIS (AD): A DOSE ESCALATION STUDY. S. Kang and the Tacrolimus Ointment Study Group, University ofMichigan, AM Arbor, MI A multicenter, randomized, double-blind, vehicle-controlled(V), sequential group, dose escalation study was designed to evaluate the safety and efficacy of 0.03%, 0. I%, 0.3% TO in adults with moderate to severe AD tiecting at least 76% of their total body surface area (BSA). Patients (n=26) applied study drug BID for a maximum of 3 weeks No patients in the V or 0.03% groups versus 100% in patients in the 0.1% and 86% in pat&s in the 0.3% groups had marked or excellent improvement at the end of treatment (BOT). Five patients (84%) in the V group discontinued the study due to lack ofefficacy. Application of any of the three TO concentrations resulted in a greater reduction in &&ted BSA than observed with V; mean changes from baseline in BSA a&ted were: V -5; 0.03% -25; 0.1% -40; and 0.3% -53 Individual signs and symptoms of AD remained the same or worsened in the V group while improvement was observed in all patients applying TO. All three TO groups showed a decrease in a mean composite score by Day 4 which was maintained throw& _ EOT; in contrast. this score increased (worsened1 ii the-Vgroup; at EOT, mean changes from baseline in composite scores were: V group +2; 0.03% -4,O. 1% -7; and 0.3% -8. Application site adverse events (AE) were reported for 50% oftbose administered either V or TO,most ofthese AE had their onset within the first 4-5 days of treatment and subsided by Day 8. Skin burning, folliculitis and pturitus were the most common application AE Nine patients bad B peak tacrolimus blood concentration LI ng/mL. No apparent relationship between blood concentration and AE was observed. No significant changes in laboratory profile were see”. TO showed therapeutic benefit and was safe when repeatedly applied over a large portion ofthe BSA.
CYTOKINE INDUCTION IN HAIRLESS
MN and 1Umv. TexasMedicalBranch,Galveston,TX.
Imiqunnodcream 5% has recentlybecome avatlable m the US for the keeatment of external gemtal and penanal warts caused by human papdlomavirus (HPT9. One OhJective of these studms was to determme cytokine induchon followmg topwal lmlqmmcd applicahon to hanless m,ce and ma Phase I vehicle controlled study, to human gemtal wertpahents A second obJcctive of the human study was to measure effects of drug treatment on cell makers and on HPV DNA and IIPV gene expressmn m IIPV pahents. In the mouse study, bmpsies were take,, at the treatment s,te and from the other side of the mmne at the time of drug apphcatmn, at I hour and at 2 hours. In humans. hiopsles of the wart treatment site were taken at drug mihatmn, at 6 weeks and at the end of I6 weeks treatment or wart clearance. Human bmpstes were analyzed by reverse transcriptase (RT) polymerase cham reactm” (PCR) for mRNA for several cytokines, cell markers and WV genes and by PCR for IIPV DNA (copxs/cell). Moue bmpsies were analyzed for interferon alpha (EWa) and TN&a “RNA by RT-PCR and for cytokme protem levels. In mice, increases were seen m “RNA for IF&? and for IFN and TN&a protein at the treatment site but not in bmpsxs from the untreated side of the mice. In humans, nniquimod treahnent caused increases in mRNA for IPN-a, TNFa. EN-P, IF’N-7, and IL-lZp40. Since mRNA for the IFN inducible protein, Z’S’oligadenylate synthetase was Increased, we also conclude that IFN-a protem was mcreased. T-cell marker CD4 mRNA was also mcreased HPV DNA load and mRNA for HPV L I protem were slgniiicantly decreased and wart we was decreased m all patients treated wth tmlqmmcd m tlus study. These results m&c& that topical imlqmmod is an effectwe local cytokme inducer in skin and an effectne treatment for HPV lesmns m humans.
1251
1254
TREATMENT OF HIV-RELATED EOSINOPHILIC FOLLICULITIS WITH ITRACONAZOLE PRODUCES CLINICAL REMISSION AND NORMALIZATION OF PLASMA EOSINOPHILS AND IgE. Michael Maiors. Melanie Adams. Reoato Oration, Krista Sharp. Roger Wibon. Irene Dounhertv and Ponaisoo Crw Jr., Dept. of Dermatology, University of Texas Southwestern Med. Ctr, DaIIas, TX, USA. EosioophiIIc folllculitb (EF) is B markedly pnrItic disease of undetermined eticdogy that is highly prevalent in HIV+ individuaI8; eosbwphilin and high plasma IgE are assoeIatedfeatures. Itrsconazole and metronidazole hwe each been reported to be etlicacious treatments, although neither drug has been subjected to controlled study. Demodex mites have been causally Implicated, although the organism la insensitive to itrneonuole or metronidazole. To evaluate therapeutic &lacy, we conducted P prospective trial in which HIV+ patients who fulfilled strict clinical, histologic and laboratory criteria for EF (including culture of lesional skin negative for bacteria and fungi) were randomized to 3 peroral treahnents for 4 rks: itraconazok (ZOOmR BID), met~cmidszole (500 mg BID),.and an mti-mite agent, lvermectin (200 pg/wk). butcomes were evaluated in double-blinded fashion nt 0.2.4 and 8 wks. and analvzed using repeeted measurer of vsriance and the KruskaI-Wallace test. Itracon&Ie-treated patients had significantly reduced mean lesion counts and extent of &In involvement, Iasting at least 4 wka past treatment termination. This remission was paralleled by normnlization of ewinophllin and plasma IgE, and improvement in 4 of IO quality-of-life meswres (itching, mood, &In health, and productivity at work). By eontmst, metronidazole- or ivermectln-treated patients exhibited either no change or deterioration in these parameters. These studies represent the first controlIed, randomized and doubkblinded validation of the efticacy of itraeooazole In the treatment of HIV-related EF. Our findings indicate that itrsconazole exerts P beneficial immunologic effect separate from its known anti-fungal actIvIty.
CETIRIZINE ;F-zB ran
INHIBITS
AzT!VAT!ON Lou s
ette J an
TNFa-INDUCED
IN ,HUMAN
. JeawP~uxP.
VCAM-1 EN?OhTEELIAL
EXPRESSION CELLS IN
AND VITRO.
e . . me_ M, elMelac~ Pierre G ras*. Louis D”bettret* and Laurence Micbcl*. •INSE~~M ~312, Latmratoire & Dcrmamlogie, H*pital Saint-Louis. Pais;%CB Pharma S.A.. Nantme, Prance. Cetirizine is a potent HI-receptor antagonist that possesses
anti-inflammatory properties like modulation of eosinopbil infdhation in viva in cutaneous sites following allergenchallenge. Cetitizine has been shown to reduce the expression of intercellular adhesion molecule-l (ICAM-1) on conjonctivalepitbelial cells in viva after antigeoic stimulation. To better caracterize the mechanism of action of cetirizine on adhesion molecule expression, we investigated the in vim effect of cetirizine on cytokineinduced expression of vascular cell adhesion molecule-l (VCAM-I). E-selectin @LAM-I) and ICAM-I in cultured human umbilical vein endotbelial cells (HUVEC) using immunohistochemistry, cytofluorimetty and quantitative ELISA. The neahnent with cetbizine (10mt3Mto lOAM) had littleeffect on ICAM-I and ELAM-I expression. However, the expression of VCAM-I on HIJVBC stimolatedby either IO or 100 U/ml of TNFa during 16 hours was significantly reduced by cetirizine hzatmem according to a dose-dependent manner. TNFa-activation of VCAM-I tmnscription in endothclial cells depends on the activationof NF-rB-like transcriptional proteins. Therefore, we explored the mode of action of cetirizine on NF-xB activation using electrophoretc mobility shift assay (EMSA). Our results clearly demonstrated that, according to a dose-dependent manner. cetirizbx treatment inhibited the activation of NF-xB induced by IO U/ml of TNFa in HUVEC. Slmilarresults were obtained using human damal mJcrovascularendotbeIiaI cells. In conclusion. “or work demonstrates that cet&ioe modulates VCAM-I expression on vascularendotbelial cells by acting at the level of gene transcription. By inhibiting activationof the transcription factorNF-rB, cetirizine might regulate the proinflammatory response of endothelium within tissues.