Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment.
BACKGROUND
Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP).


OBJECTIVE
The objectives of this study were to observe the effect of budesonide on the expression of IL-1beta, TNF-alpha, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-alpha, GR-beta, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response.


METHODS
Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR.


RESULTS
There was a significant decrease in the expression of TNF-alpha (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1beta (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1beta (4.18 vs. 0.42; P<0.005) and GR-beta (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group.


CONCLUSIONS
Topical budesonide reduced the expression of TNF-alpha, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1beta, ICAM-1 and nuclear factor (NF)-kappaB at diagnosis and higher expression of both IL-1beta and GR-beta after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1beta, ICAM-1 and NF-kappaB may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-beta in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease.
Valera
F C P
FC
Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. facpvalera@uol.com.br
Queiroz
R
R
Scrideli
C
C
Tone
L G
LG
Anselmo-Lima
W T
WT
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance; D004724:Endoscopy; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology; D009298:Nasal Polyps / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D019819:Budesonide